B Q,UK. 0QH, CB2 avyT McMahon T. Harvey glance a at curvature Membrane GLANCE A AT SCIENCE CELL ß 1 that process active an is curvature and membrane and local sensing article high generating, to maintaining Glance how help a summarize at we could Science poster, Cell membranes accompanying is this complex In It subregions. in local functions. shapes define cellular local and that trafficking possible maintaining central for of is curvature importance of maintenance and spheres generation the either The tubules. being or defining subdomains. shapes, membrane simpler in have local intermediates parameter and Transport organelles important cells, of an morphology is curvature Membrane ABSTRACT Atosfrcrepnec hmmclbcma.k [email protected]) ([email protected]; correspondence for UK. *Authors 6BT, WC1E London College, Birkbeck & London R aoaoyo oeua ilg,FacsCikAeu,Cambridge Avenue, Crick Francis Biology, Molecular of Laboratory MRC 05 ulse yTeCmayo ilgssLd|Junlo elSine(05 2,16–00doi:10.1242/jcs.114454 1065–1070 128, (2015) Science Cell of Journal | Ltd Biologists of Company The by Published 2015. 2 nttt fSrcua n oeua ilg,Uiest College University Biology, Molecular and Structural of Institute 1, n maulBoucrot Emmanuel and * 2, * elo rael hp,lclcrauecnafc rcse like and concentration membranes. processes protein on as affect activation well enzyme can as fusion curvature and local scission membrane shape, providing organelle to addition or in cell where curvature, membrane of about functions discoveries the the of by some and summarize polymerization also We by motors. generated molecular forces with cytoskeleton scaffolding of the macroscopic by (v) insertion finally, and, reversible domains (iii) protein oligomerized hydrophilic by crowding, scaffolding nanoscopic domain (iv) motifs, protein (ii) or hydrophobic asymmetry, protein membrane and or general integral of proteins composition using domains transmembrane lipid proteins shaped of in specialized partitioning changes by (i) controlled mechanisms: and mediated is E OD:Apiai ei,BRdmi,Blyrasymmetry, curvature Bilayer Membrane domain, Lipids, BAR helix, Amphipatic WORDS: KEY 1065

Journal of Cell Science ebae r osatytre vrb trafficking by Lipid life. eukaryotic over high- for generate necessary to of turned is ability Because compartments thousands the life. tubules), curvature constantly the or eukaryotic (vesicles of intermediates are for coordination required membranes timely reactions and supporting biochemical thereby compartments complex proteins, membrane compartmentalize the to intracellular cell many the allows of formation The Introduction GLANCE A AT SCIENCE CELL 1066 and headgroup artificial bulky the in a as overall 2014). such al., of chains, the 1,2-dioleoyl- et polar acyl lipids Pinot combination both defines the 2014; of saturated al., of monounsaturation saturation artificial et its size (Vanni chain than lipids The the the space acyl of between more geometry chain and ratio occupy the in the to headgroup kink a Thus, it induces forces counterpart. acid) oleic thus in and as (such bond double 2006). Kozlov, and Zimmerberg 2006; Camilli, De and the Paolo Di 2003; of Kozlov, away and bending Chernomordik monolayer in (reviewed the the headgroups bending the in from favoring inverted curvature, positive thereby a headgroups lipids, an into in the membrane confers as large to together. shape such (PtdIns) conical the closer ratio, phosphates chain come or acyl phosphatidylinositol headgroups to (LPC) the headgroup bends lysophosphatidylcholine that large lipids fashion such a a Conversely, a with impose thus monolayer such and a shape in conical where roughly curvature, a than negative headgroup have polar PtdCho, smaller of a as that have such which Lipids cardiolipin, monolayer. or (DAG) flat a diacylglycerol form acid, phosphatic phosphatidylethanolamine (PtdEtn), that lipids cylindrical 1996). are lipids al., et constituent Leikin their 1992; of al., curvature et spontaneous (Kozlov and weighted the the inner the by of dictated its to average themselves of equal are which curvatures curvature monolayers, spontaneous spontaneous outer a the (see adopt between bilayer shape will difference 2006). to bilayer Deserno, change and a Cooke also Owing Thus 2005; might Gallop, lipids. and membrane (McMahon the local poster) whole adopt the will the monolayer of coupling, with a lipids curvature then and many together, spontaneous If (length monolayer. cluster their the shape on of compositions similar shape packing, size a side-by-side chain imposing their the thereby determine acyl features on These their depending saturation). and shapes intrinsic headgroups have asymmetry and Lipids composition lipid in Change stabilization generation provide and curvature others membrane of whereas membranes. Mechanisms on lipids, tension impose changing that proteins forces by are and directly scaffolding there or generating addition, act sensing, In contain that in curvature. specialized proteins membrane are Many stabilizing that have motifs elastic evolution. these or them; throughout domains shape have to conserved and, required bending membranes been are spontaneous mechanisms to active cell resistant thus, them make eukaryotic that properties forming bilayers Tae lpdfipss httasoaepopoiis(e.g. phospholipids translocate that flippases) (lipid ATPases thus and 2008). cylindrical PtdCho, (Ikonen, of of curvature and spontaneous packing sphingomyelin) disfavor the as (such increase sphingolipids sterols Antonny, Conversely, and (Bigay 2012). curvature spontaneous favors NTA-DOGS, clcanstrto loifune ii emty any geometry; lipid influences also saturation chain Acyl (PtdSer) phosphatidylserine and (PtdCho) Phosphatidylcholine ciemitnneo ii smer ytp VP-type IV type by asymmetry lipid of maintenance Active sn gyeo3popoeie(OS rNi or (DOPS) -glycero-3-phosphoserine 2+ - h eeaino eaiemmrn uvtr Eese l,2010; al., et Ro (Ewers by with curvature coincides membrane negative and of leaflet inverted lipids generation one (conical, the favors on shape poster) B, certain same see cylindrical; toxin the or Shiga conical with of or lipids and B of clustering toxin concentration Graham cholera the the as in such toxins, Finally, (reviewed bacterial also curvature 2010). sphingomyelinases membrane Kozlov, lysophospholipid or local by monolayer A induce one phospholipase of Changes leaflets 2009). composition acyltransferases, al., two lipid et Xu the the 2009; al., between a in et lipids Ruaud generating 2008; al., of by et partitioning (Poulsen budding the vesicular in and difference curvature membrane changes supports in 2008) al., the et to Devaux 2007; leaflet (Daleke, extracellular face cytosolic the from directionally PtdEtn) or PtdSer hr h ebaebnsaa rmtesd ihtelargest the with side the crowding from protein away Thus, bends by bending. membrane bending the in membrane where result cause also might might receptors MacKinnon, domains proteins extramembrane 2014; transmembrane of conical al., asymmetry of et The inverted 2005). 2014; Fribourg and Unwin, al., or 1974; 2003; et Salpeter, (Aimon conical transporters membranes and associated intrinsic Fertuck their channels, an bend can have shape (ion that receptors) proteins crowding protein and Transmembrane domains transmembrane shaped of Partitioning hogotteetr el uha pi,endophilin, epsin, barkor, NUP133, as ArfGEF TRIP11), Arf ArfGAP1, as known ARHGAP17), GRK5, such (also GTPases, as GMAP-210 atlastin GBF1, known remodeling cell, and (also Sar1 membrane proteins, nadrin in entire Bin2, involved amphiphysin, the are present are that helices throughout proteins Amphipathic resulting many 2010). al., the et al., in (Campelo et assemblies), pronounced McMahon same more protein 2008; much the if is complex (within curvature but proximity within membrane space, close in or in the rapidly held insertion, protein dissipated single the are is a of insertions is membrane thickness several bilayer there the (the the If small of of 2002). center is bending al., the this curvature et in membrane, of (Ford is the radius monolayer) local wedge of the the inducing part thus, of outer and, apex of the the that in given way that ‘wedge’; is means a efficient insertion as the shallow acts very between It the poster). in a (see motif curvature is membrane protein headgroups hydrophobic small lipid a of unclear motifs Insertion protein still hydrophobic of is Insertion 2014). mechanism al., et this Kozlov 2012), membrane in of al., discussed induce et contribution (recently (Stachowiak to the mechanism the suggested crowding to although a bind been by that sorting has proteins curvature trafficking in of surface membrane role concentration from) local membrane a high them play A excluding might carriers. (Ehrlich (or mechanisms pits into membrane These receptors clathrin-coated of 2004). into forming al., generation of receptors, et stabilizing the scaffolding by supports (LDL) local curvature pits lipoprotein in endocytic low-density as forming results among such or receptors, which integral transmembrane directly transferrin of 2005), clustering many 2000; The either al., al., membranes. addition, et et (Boudin – In proteins Eckler connecting 2012). through oligomerize or themselves al., proteins et membrane (Copic domains nlntsadi hi fiiisfrcagdlpd dcae ythe by (dictated lipids sorting charged for affinities endosomal vary their helices in and Amphipathic the lengths 2010). in Antonny, CHMP4B and and protein Drin in (ESCRT)-III Atg3 (reviewed transport for B12, required complexes annexin synuclein, mre l,2007). al., et ¨mer ora fCl cec 21)18 0517 doi:10.1242/jcs.114454 1065–1070 128, (2015) Science Cell of Journal a -

Journal of Cell Science htte a moeteritisccrauelclyo the on locally curvature intrinsic their likely impose thereby more can it interactions, makes they which ‘side-to-side’ that concentration, or local their oligomerise ‘tip-to-tip’ increasing further can forming domains BAR by Some 2011). Haucke, and h 2dmiso yattgi- n o2 Gofne al., et (Groffen Doc2b and synaptotagmin-1 of subcellular domains ancient C2 2009). their very al., the a et for Ramamurthi is 2009; al., sensing helices et curvature (Lenarcic induce amphipathic mechanism that or suggesting use sense targeting, to DivIVA SpoVM, as abilities such proteins, varying or bacterial of have Several face curvature. thus hydrophobic the membrane and of edges helix), the on the acids amino the of nature GLANCE A AT SCIENCE CELL mn cd lsn ragnn)o h A oueand module BAR phosphatidylinositol the and/or PtdIns(4,5) of as [PtdSer arginine) such lipids phosphates, or charged (lysine negatively charged acids positively is binding between amino initial prototypical interaction The electrostatic 2004). membrane The al., by to et mediated (Peter membranes. binds face which concave to its amphiphysin, crescent-shaped through is bind protein are domain that BAR domains modules dimeric (Bin/Amphiphysin/Rvs) BAR del and domains BAR Parton 2011; endoplasmic 2009). al., al., the et et and Shibata 2013; (Hu caveolae Pozo, respectively at (ER), curvature formation the reticulum of facilitating stabilization the thereby of as membranes, or or proteins) into presence flotillins insert bridging as the through caveolin, well or in as (directly least oligomerize such reticulons at Proteins tension. efficiently, 2012; membrane assemble pre-existing al., a to self- requires et dynamin curvature Praefcke dynamin However, Faelber 2013; by 2004). Roux, the McMahon, and the in Morlot and curvature 2012; to Camilli, of (reviewed assembled De and membrane shape spirals Members Ferguson the this into induce 2012). of polymerizing of al., superfamily rigidity transmission et GTPase the the (Copic to and on membrane bind coat not depends to bend polyhedral to them do proteins membranes link coat and the They to of to proteins capacity 2012). The McMahon adaptor poster). on (see al., membranes rely 2000; et and directly Kirchhausen, Zanetti membrane 2011; 2011; factors Boucrot, key Schekman, (Jensen are budding COPII vesicle and during and curvature COPI membrane clathrin, stabilize that as such proteins Coat level. oligomerization microscopic Protein the oligomer the at by curvature formed membrane is affect that thus shape into and a assemble have also that might structures proteins larger imposed Nanoscopic is membrane. interface domains), the membrane-binding protein on the of of scale shape the the on whereby (curvature curvature level nanoscopic membrane a supports at proteins peripheral domains by protein hydrophilic Scaffolding oligomerized by scaffolding Nanoscopic Ca a al., in et membrane (McMahon to curvature bind of domains C2 degree As high curvature. C2 2010). bilayer, a of lipid induce the generation into domains the insertion extensive to their oligomerization Plomann with contribute protein Consistent 2007; case, also latter al., scaffolding the membrane et in and induce (Daumke although, 2010); also wedges al., as EHD2 membrane- et the acting and at by Pacsin or 2007) curvature of al., et interface Martens binding 2009; al., et Hui 2010; ta. 09 atn ta. 2007). al., et Martens (Hui 2009; regulated al., tightly is et activity bending membrane their manner, h neto fhdohbclosta r rsn ttetpof tip the at present are that loops hydrophobic of insertion The P 2 MmadUgr 02 Rao 2012; Unger, and (Mim ] 2+ -dependent ta. 04 oco ta. 2012). al., et (Peter Boucrot scission disfavor 2004; membrane and al., for et needed tubules curvature membrane extreme of more BAR the formation 2011). the Haucke, and favor Rao domains 2012; Unger, and (Mim membrane lgmrcpoensafl hti en edtgte ythe an by within together held 2011). occur Boucrot, being and all is (McMahon coat that – clathrin scaffold or (epsin) protein (amphiphysin) inserting oligomeric membrane modules – addition, proteins in scaffolding several have, by which clustering of their some and leaflets membrane two rael opoois(..E,Gliadendosomes) and Golgi 2010). ER, al., et Leduc (e.g. in (reviewed the induces morphologies of membrane underlying also some myosin supports Active organelle and and an reorganization dynein 2008). membrane kinesins, providing considerable by McMahon, pushing it or by and and membrane pulling 2010; intervals, (Doherty shapes regular cell Baum, at scaffold macroscopic bilayer maintains and the to cytoskeleton imposes (Rohn connecting cellular cones) The by tension specialized visual 2001). in or Sheetz, or (neurons ruffling) during rounding), shapes cell membrane (membrane mitotic plasma supporting the actin phagocytosis cortical of (i.e. arrangement division specific lamellipodia, cell the and the the filopodia as of in macroscopic such membrane or the plasma at mediates organelles, the also of cytoskeleton intracellular radius), curvature The curvature large in ER. the microns in or multiple Golgi present membrane of is range the which cell (in scale microtubule macroscopic and supports filament intermediate cytoskeleton actin, the by cytoskeleton Scaffolding the by scaffolding Macroscopic iohnra iso rfso)o h auaino the (e.g. of cell maturation the the of or needs the fusion) to or according fission dynamic, are change mitochondrial shapes (Shibata they characteristic these carriers and However, secretory 2009). droplets, and al., lipid the et endosomal mitochondria, to Golgi, or rise the ER, give autophagosomes the which of curvature, shapes extent membrane typical the of by morphology mediated membrane localization are their and shapes by These characteristic recognizable micrographs. electron easily have in them make organelles that shapes intracellular Most shaping Organelle al., et Shibata 2005; Gallop, and local (see 2009). McMahon dependent fusion, in shape and be reviewed also fission poster; might control reactions their enzyme to to or to the ability tethering related be the central and to indeed, likely compartmentalization, function; are is organelles for of transport shapes shapes high-curvature necessary characteristic of membrane is formation the intermediates biological Thus, life. of eukaryotic control The curvature membrane of Functions mechanisms of PtdIns(4,5) partitioning and membrane-bending asymmetrical [PtdSer The lipids the conical place. of inverted take clathrin- a above several of presented formation pit, the during combine and coated example, (McMahon that For curvature interactions cellular 2005). of of Gallop, same stabilization network and the a induction in form sensing, involved thus, are and, that sculpting. process to proteins bind membrane both other or induce mechanisms abilities numerous scaffolding efficiently aforementioned motifs, insertion to the with Proteins place of takes several usually of combination mechanisms A multiple of action Synergistic ora fCl cec 21)18 0517 doi:10.1242/jcs.114454 1065–1070 128, (2015) Science Cell of Journal P 2 ewe the between ] 1067

Journal of Cell Science nognlefo t ebaeo rgn hl avoiding while origin, of membrane its and separate to from localized membranes bilayer organelle the two of requires an trans in membranes connection two timely between Scission 2011; scission al., Membrane et Haucke 2008). 2014; Marshall, Nunnari, and Rafelski and synaptic or (Friedman endocytic of vesicles) consumption or formation (e.g. organelle GLANCE A AT SCIENCE CELL ta. 00 u ta. 09 atn ta. 07 na tal., et 1068 Snead 2007; al., (Groffen et Martens synapses 2009; al., neuronal et 2014). Hui at 2010; fusion al., release membrane helix et accelerate amphipathic neurotransmitter and the facilitate coordinated and or domains which the proteins, C2 complexin, Doc2 the and of and as both membrane such synaptotagmin by modules, the of membrane-bending aided of of be composition action McMahon, might and lipid complexes Martens the assembly SNARE 2006; the upon Scheller, However, bring and proximity 2008). that (Jahn close poster) complexes into (see SNARE membranes cognate apposing of mediated two is assembly membrane target the its and by vesicle a between fusion during The fusion membranes Membrane (Sawa-Makarska cargo Atg8-coated the 2014). al., around of et wrapping and synergy bending autophagophore Atg19 the receptor autophagy and during the membrane 2011), by 3-kinase al., recruitment subsequent cargo phosphatidylinositol et curved the between (Fan mediates III adaptor highly biogenesis that class autophagosome autophagosome-specific Atg14L) the of as the recruitment are known by (also examples attachment barkor of sensing Other NSF fidelity the membrane soluble targeting. increasing incoming of thereby vesicle on (SNAREs), engagement curvature receptors high the protein sense before 2007; tip to the al., strings at vesicles et helices molecular amphipathic (Drin uses long Golgi protein of cis This 2008). the al., vesicle the at et as in Drin acts such that role proteins GMAP-210 tethering important through Golgin exerted an is has which targeting, sensing curvature Membrane tethering and targeting 2013; Membrane al., et these 2010). bodies (Buchkovich in al., multivesicular helices et involved Rossman of amphipathic proteins formation key have because the processes endosomes, in exosome and in as virus 2012). (MVBs) in well role al., a as et have to budding, (Boucrot likely can also pits case which is epsin, the mechanism clathrin-coated and This is 2005) at it al., dynamin et as creating (Lee scission, support vesicles favor COPII by to at Sar1 bilayer vesicles for the the membrane-trafficking on supports stress hydrophobic nascent carriers sufficient and vesicle of of constricted Praefcke of concentrations fission 2012; neck local the Camilli, at De High insertions and 2004). (Ferguson detachment McMahon, and vesicle neck the the of lipid and, of scission two vesicles the the between causing nascent fusion membrane thereby trigger of bilayers, of they neck GTP, drivers of the hydrolysis main 2012; at upon the Camilli, oligomerize are They De Members superfamily scission. 2013). and dynamin Lamb, (Ferguson and the Rossman budding of 2010; virus Hanson, and in Hurley as coat), well coat), clathrin endosomes of (AP-2 as (COPI membranes coats), budding plasma Golgi clathrin and the coat), complexes) AP-3 (ESCRT and (COPII in (AP-1 ER step network the key trans-Golgi from a vesicles is coated scission Membrane leakiness. as nw sKsp sas rae tahg ebaecurvature membrane high a at greater al., also is Kes1p) et Osh4p as transporter known (Chang-Ileto (also sterol the membrane of a For capacity curved lipid-extraction The has highly 2011). activities. synaptojanin on activity phosphatase curvature-sensitive higher phosphoinositide display the instance, enzymes Several activation protein and Enzyme 2012). recycling al., and et sorting Okamoto 2012; endosomal Korswagen, or and sites (Cullen exit the ER for important of also the organization is proteins, Sar1, nexin of sorting as or concentration complex such The ESCRT proteins, bud. -inducing intrinsic the an leave and have to high-curvature-sensing or them bud the forces to do that them either curvature localize bud to that the adaptor proteins an favor exclude have not to that help proteins alternatively, concentrate or, Unwin, curvature to bud initial help 2003; the might intermediates, MacKinnon, formation trafficking 1974; vesicle making nicotinic Salpeter, In 2005). al., for and et (Aimon and Fertuck poster) case regions Ca (see 2014; curvature post-synaptic membrane as the high at of concentrate well areas be other to as appear might receptors that channels glutamate This and shapes. acetylcholine accommodate relevant that mediate membrane the might the of receptors regions into transmembrane partitioning of their shapes intrinsic The sorting Protein io,S,Cla-oe,A,Brhu,A,Pnt . ome,G .and E. G. Toombes, M., Pinot, A., Berthaud, A., Callan-Jones, S., Aimon, References online the available in http://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.114454/-/DC1. are downloading at panels files for poster JPEG Individual available jcs.biologists.org. as at is article poster this of the version of version high-resolution glance A a at science Cell for PMC in Deposited months. E.B. 6 to a Medicine after and Preventive release for BB/I018921]; Institute number Lister the [grant Research from Fellowship Sciences prize Research Biological number Phillips and [grant David Biotechnology grant Council a UK Council and H.T.M.; Research Medical to a U105178805] by supported was work This Funding interests. financial or competing no cellular declare authors further The that curvature. interests membrane and Competing on future depend to near recognized the be will in functions uncovered fusion. shaping very be membrane and is as underlying will it mechanisms scission cells, additional such eukaryotic that budding, within likely universality processes, vesicle its with and remodeling Consistent shaping the membrane membrane concert local organelle to in complex high utilized inherent be a can during mechanisms generate are these or of allow that Several stabilize that curvature. sense, properties exist to mechanisms lipid distinct proteins several the bilayer, to membrane addition In perspectives and Conclusions membrane by activation protein will of curvature. work instances future that Lee other likely is 2008; by many It (GEFs) al., uncover 2008). activated al., et factors et Krauss Lundmark 2005; also 2005; exchange al., et al., are guanosine et (Bigay (GAPs) their curvature membrane proteins of GTPase-activating Sar1, some and Arl and as Arf, GTPases well small The 2014). as al., GABARAP et the (Nath or of Atg3 lipidation MAP1LC3A) by is by as (encoded 2007), LC3 al., protein et autophagy Drin 2011; al., et Saint-Jean (de distribution. P. Bassereau, ora fCl cec 21)18 0517 doi:10.1242/jcs.114454 1065–1070 128, (2015) Science Cell of Journal e.Cell Dev. 21) ebaesaemdltstasebaeprotein transmembrane modulates shape Membrane (2014). 28 212-218. , 2+ rK or +

Journal of Cell Science eax .F,Hrmn,A,Olen .adKzo,M M. M. Kozlov, and N. Ohlwein, A., Herrmann, F., P. B., Devaux, Payrastre, G., Chicanne, D., Douguet, V., Delfosse, M., Saint-Jean, de ame . udak . als . atn,S,Bte,P .adMcMahon, and J. P. Butler, S., Martens, Y., Vallis, R., Lundmark, O., Daumke, aee .L. D. Daleke, uln .J n osae,H C. H. Korswagen, and J. P. Cullen, oi,A,Lta,C . olek .A,DAcneo .G n ilr .A. E. Miller, and G. J. D’Arcangelo, A., M. Horlbeck, F., C. M. Latham, A., Deserno, Copic, and R. I. Cooke, Chernomordik,L.V.andKozlov,M.M. hn-lt,B,Fee .G,Ca,R . ooo,S . ox .adDi and A. Roux, V., S. Voronov, B., R. Chan, G., S. Frere, M. B., M. Chang-Ileto, Kozlov, and T. H. McMahon, F., Campelo, D. S. Emr, and S. Tang, and M., P. W. Worley, Henne, J., L., N. R. Buchkovich, Huganir, R., Shigemoto, J., Xia, A., Doan, H., Boudin, oco,E,Pc,A,C A., Pick, E., Boucrot, rn . ael,J . ate,R,Bemr . cwrz .U n Antonny, and U. T. Schwartz, T., Boehmer, R., Gautier, F., J. Casella, G., Drin, P. Camilli, De and G. Paolo, Di ia,J,Csla .F,Di,G,Msi,B n non,B. Antonny, and B. Mesmin, G., Drin, F., J. Casella, J., Bigay, B. Antonny, and J. Bigay, GLANCE A AT SCIENCE CELL rn . oel,V,Csla .F,Guo,P n non,B. Antonny, and P. Gounon, F., J. Casella, V., Morello, G., Drin, B. Antonny, T. and G. H. Drin, McMahon, and J. G. Doherty, a,W,Nsii .adZog Q. Zhong, and A. Nassiri, W., Fan, Noe V., Haucke, Y., Posor, S., Gao, M., Held, K., Faelber, Mancini, W., Chai, S., Dmitrieff, K., Bacia, E., A. Smith, W., L. Romer, M. H., Ewers, Nibert, K., Chandran, R., Hariharan, A., Oijen, Van W., Boll, M., Ehrlich, M. Gautam, and R. Kuehn, A., S. Eckler, rbug .F,Cai . ozn,C .S,Gblii . aaii . Marco, R., Marabini, F., Gubellini, S., O. C. Sorzano, and M., R. Chami, P. F., P. Evans, Fribourg, J., G. Praefcke, Y., Vallis, J., B. Peter, G., I. Mills, G., M. Ford, M. M. Salpeter, and C. H. Fertuck, P. Camilli, De and M. S. Ferguson, lpae a ouaemmrn structure. membrane modulate can flippases bilayers. 978. lipid G. between Drin, 4-phosphate and phosphatidylinositol B. Antonny, W., Bourguet, novdi ebaeremodelling. membrane in involved T. H. ermrdpnettafcigevents. trafficking retromer-dependent 21) Rcropoete pcf eurmn o OI otrigidity coat COPII for requirement a specify Sec13p. properties by cargo mediated ER (2012). curvature. membrane membranes. biological of fission 207. and fusion in 218. ymmrn uvtr n aiiae ebaefission. membrane facilitates and curvature membrane by G. Paolo, proteins. by generation curvature J. membrane of mechanism insertion site. binding domain PDZ M. A. Craig, 136. emnlisrinmtfacosteECTIIflmn uigMBvesicle MVB during filament ESCRT-III the anchors formation. motif insertion terminal domains. BAR crescent by restricted is and M. helices amphipathic M. Kozlov, and B. 1591-1600. epnst ebaecrauetruhtefligo ii akn sensor packing lipid a of folding the through motif. curvature membrane to responds specificity. determining in Cell territories cellular defining organelles: membrane 21) tutrlisgt nodnmnmdae ebaefission. membrane dynamin-mediated 20 into insights Structural (2012). al. et infection. L. and 12 Berland, invagination V., membrane SV40-induced Chambon, determines J., Kartenbeck, R., pits. clathrin-coated of T. Kirchhausen, and of clustering on effects negative dominant rapsyn. has full-length and clustering disrupts golgin. domains a by membranes lipid curved and 320 flat of tethering Asymmetric curvature. Lett. FEBS interactions. 37 membrane-cytoskeleton of consequences dynamics. membrane . al,J .adLe and M. J. Jault, S., Nature T. H. McMahon, endplates. motor mouse USA Sci. at Acad. binding Natl. alpha-bungarotoxin 125I-labeled by GTPase. Barkor/Atg14(L). by 108 sensing curvature membrane atra utdu B rnpre na nadfcn ofrainadi a in and conformation inward-facing an in environment. transporter lipidic ABC multidrug bacterial 1621-1628. , 11-18. , 65-95. , 95 670-673. , 7769-7774. , 20) eea amphipathic general A (2007). 23 2325-2339. , MOJ. EMBO 20) rhtcua n ehnsi nihsit nEDATPase EHD an into insights mechanistic and Architectural (2007). 886-895. , 419 a.Rv o.Cl Biol. Cell Mol. Rev. Nat. e.Cell Dev. a.Src.Ml Biol. Mol. Struct. Nat. 21) yatjnn1mdae I45P yrlssi modulated is hydrolysis PI(4,5)P2 1-mediated Synaptojanin (2011). 361-366. , 584 20) hshlpdflippases. Phospholipid (2007). 20) rsnpi lseigo Gu7 eurstePICK1 the requires mGluR7a of clustering Presynaptic (2000). 1840-1847. , 24 Neuroscience 2244-2253. , 20) uvtr fcahi-otdpt rvnb epsin. by driven pits clathrin-coated of Curvature (2002). .Ml Biol. Mol. J. 27 ´vy, D. mee . ik,N,Eege,E,MMhn .T. H. McMahon, E., Evergren, N., Liska, G., amdere, ¸ 71 21) ebaefsini rmtdb neto of insertion by promoted is fission Membrane (2012). 20) noyoi yrno ntainadstabilization and initiation random by Endocytosis (2004). Science ipy.J. Biophys. Nature Cell 201-214. , 1376-1378. , 21) mhpti eie n ebaecurvature. membrane and helices Amphipathic (2010). 21) uvtr,lpdpcig n lcrsaisof electrostatics and packing, lipid Curvature, (2012). Neuron 118 21) Dcy-lcrnrcntuto fBr,a BmrA, of reconstruction cryo-electron 3D (2014). 443 335 20) hshioiie ncl euainand regulation cell in Phosphoinositides (2006). 591-605. , 426 131 14 20) opigbtenlpdsaeand shape lipid between Coupling (2006). 651-657. , 17) oaiaino ctlhln receptor acetylcholine of Localization (1974). 91 28 1359-1362. , 13 21) yai,amembrane-remodelling a Dynamin, (2012). 138-146. , 21) otn eispoiedvriyfor diversity provide nexins Sorting (2012). Nature 2059-2069. , 487-495. , 661-670. , 485-497. , 75-88. , a a.Cl Biol. Cell Nat. 21) uohgsm agtn and targeting Autophagosome (2011). hlclmtffrsnigmembrane sensing for motif -helical 20) eito,mdlto,and modulation, Mediation, (2008). 20) eeino -emnlrapsyn N-terminal of Deletion (2005). 21) s4 xhne trl for sterols exchanges Osh4p (2011). 449 .Bo.Chem. Biol. J. 20) rti-ii interplay Protein-lipid (2003). 923-927. , nu e.Biochem. Rev. Annu. ici.Bohs Acta Biophys. Biochim. rc al cd c.USA Sci. Acad. Natl. Proc. 20) h hydrophobic The (2008). 14 29-37. , 21) M structure GM1 (2010). ,F n ame O. Daumke, and F. ´, .Cl Biol. Cell J. nu e.Biophys. Rev. Annu. 21) seta N- Essential (2013). 282 e.Cell Dev. 20) o lipid How (2008). 20) ArfGAP1 (2005). 821-825. , Cell a.Cl Biol. Cell Nat. 195 149 Structure Biophys. 20 72 Science (2008). 206- , 175- , 965- , 124- , 1778 Proc. Dev. , rus . i,J . ox . ek . iln,F . eCmli .and P. Camilli, De T., F. Wieland, R., Beck, A., Roux, Y., J. Jia, M., and J. Krauss, S. Marrink, V., L. Chernomordik, N., Liska, F., Campelo, M., M. Kozlov, H. R. Scheller, and R. Jahn, E. Ikonen, I. P. Hanson, R. and E. H. Chapman, J. and Hurley, M. F. Dunning, J., Yao, P., C. Johnson, E., Hui, A. T. Rapoport, and A. W. Prinz, J., Hu, ekn . olv .M,Fle,N .adRn,R P. R. Rand, and L. N. Fuller, M., M. Kozlov, S., R. Leikin, Schekman, and M. Ravazzola, E., Futai, S., Hamamoto, L., Orci, C., M. Lee, Campa C., Leduc, atn,S,Kzo,M .adMMhn .T. H. McMahon, and M. M. Kozlov, S., Martens, R. MacKinnon, olv .M,Kzi,P .adPpv .V. S. Popov, and I. P. Kuzmin, M., M. Kozlov, T. Kirchhausen, R. Schekman, and D. Jensen, J. S. Sigrist, and E. Neher, V., Haucke, Dı S., Martens, J., A. Groffen, cao,H .adGlo,J L. J. Gallop, and T. H. McMahon, E. Boucrot, and T. H. McMahon, T. H. McMahon, and S. Martens, T. H. McMahon, and J. B. Peter, Y., Vallis, J., G. Doherty, R., Lundmark, rhm .R n olv .M. M. Kozlov, and R. T. Graham, atn .G n e oo .A. M. Pozo, del and G. R. and Parton, R. Hirata, S., C., Nag, Saito, K., M., Matsuura-Tokita, W. K., Kurokawa, Fong, M., G., Okamoto, Puente, V., Shteyn, J., Dancourt, S., Nath, A. Roux, and S. Morlot, M. V. Unger, and C. S. Mim, Martens, and M. M. Kozlov, T., H. McMahon, J., Errington, J., L. Wu, M., Shaw, L., Visser, S., Halbedel, R., Lenarcic, lmn,M,Wtmn,J .adRdlh .G. M. Rudolph, and G. J. Wittmann, M., Plomann, T., Ferreira, A., L. and Payet, S., R. P. Lacas-Gervais, S., Evans, Pagnotta, J., S., P. Vanni, Butler, M., Y., Pinot, Vallis, G., I. Mills, M., H. Kent, J., B. Peter, remn .R n unr,J. Nunnari, and R. J. Friedman, r aiypoen ncraueaqiiina ie fvscebudding. vesicle of sites at acquisition curvature in proteins family Arf V. Haucke, Biol. T. H. McMahon, 35-45. Biol. Cell Mol. Rev. neck. the in all in it’s machinery: step ESCRT critical a is membrane target fusion. the Ca(2+)-regulated of bending Synaptotagmin-mediated Cell fdaygyeo nsrcua n lsi rpriso phospholipid of properties elastic and structural on membranes. diacylglycerol of the vesicle. completes COPII and curvature a membrane of initiates fission helix N-terminal Sar1p (2005). motors. molecular by formation Acta nanotube Biophys. membrane of Mechanism Chem. rtuin ya lcrcfed hroyai analysis. thermodynamic a field: electric an by protrusions 187-198. glance. Biol. Cell Mol. Rev. Nat. endocytosis. and exocytosis synaptic al. neurotransmitter et spontaneous G. for J. Borst, sensor Y., Ca2+ Takai, high-affinity L., release. R. a Habets, is A., Doc2b N. (2010). Goriounova, P., A. Jong, de fdnmccl ebaeremodelling. membrane cell dynamic of endocytosis. clathrin-mediated of functions fusion. membrane promotes principles. common membrane and players positive disparate generates, and by, activated is loading curvature. GTP family Arf eeaigmmrn curvature. membrane generating raiaino Rei ie nSchrmcscerevisiae. Saccharomyces in sites exit a 3412-3420. ER on of J. relies organization T. proteins A. Melia, autophagy Nakano, and of family B. Atg3. in LC3/GABARAP Antonny, domain the membrane-curvature-sensing A., of Yamamoto, Lipidation J., Bewersdorf, fission. proteins. beyond. and fusion vesicle synaptic membranes. curved negatively W. to L. Hamoen, and D. Marenduzzo, n ftePCI -A oanmycnrbt omembrane-curvature to contribute may domain F-BAR 2 PACSIN sensing. the of end oynauae hshlpd aiiaemmrn eomto n iso by fission and H. proteins. deformation Barelli, endocytic membrane and facilitate B. phospholipids Antonny, Polyunsaturated B., Goud, R., Gautier, structure. BAR amphiphysin T. H. McMahon, organizers. and protectors sensors, 505 335-343. , 147 29 ora fCl cec 21)18 0517 doi:10.1242/jcs.114454 1065–1070 128, (2015) Science Cell of Journal 283 53-60. , nu e.Biophys. Rev. Annu. .Cl Sci. Cell J. 1226-1231. , Science .Ml Biol. Mol. J. 20) ellrcoetrltafcigadcompartmentalization. and trafficking cholesterol Cellular (2008). rnsBohm Sci. Biochem. Trends ice.J. Biochem. 27717-27723. , 20) r1GPidcdtbl omto ugssafnto of function a suggests formation tubule Arf1-GTP-induced (2008). 21) ihcrauedmiso h Raeipratfrthe for important are ER the of domains High-curvature (2012). ipy.J. Biophys. 20) oasu channels. Potassium (2003). 1798 20) he ast aeavesicle. a make to ways Three (2000). s . ony .F,Pot .adBseeu P. Bassereau, and J. Prost, F., J. Joanny, O., `s, 21) ehnsssaigcl membranes. cell shaping Mechanisms (2014). 20) A oan ssnoso ebaecraue the curvature: membrane of sensors as domains BAR (2004). 327 Science 124 1418-1426. , 9 1614-1618. , 125-138. , 400 414 1-4. , 21) ebaecraueadisgnrto yBAR by generation its and curvature Membrane (2012). Cell 7 71 21) ehnc fdnmnmdae membrane dynamin-mediated of Mechanics (2013). 129-136. , 631-643. , Cell 189-194. , 2623-2632. , e rzl,R,Creis,L . ooaa N., Lozovaya, N., L. Cornelisse, R., Arazola, ´ez 345 20) NRs–egnsfrmmrn fusion. membrane for engines – SNAREs (2006). Science Science 42 138 21) ebaebdigadsiso ythe by scission and budding Membrane (2010). 122 21) OI-eitdvscefraina a at formation vesicle COPII-mediated (2011). 21) iohnra omadfunction. and form Mitochondrial (2014). 629-649. , 21) oeua ehns n physiological and mechanism Molecular (2011). 37 693-697. , 20) ebaecraueadmechanisms and curvature Membrane (2005). 709-721. , ur pn elBiol. Cell Opin. Curr. MOJ. EMBO 526-533. , 20) ehnsso ebaefusion: membrane of Mechanisms (2008). 605-617. , 21) nepa fpoen n iisin lipids and proteins of Interplay (2010). a.Rv o.Cl Biol. Cell Mol. Rev. Nat. Cell 21) aelea lsamembrane plasma as Caveolae (2013). 20) oaiaino iIAb targeting by DivIVA of Localisation (2009). 303 21) rti cfod nteculn of coupling the in scaffolds Protein (2011). 316 a.Rv Neurosci. Rev. Nat. a.Rv o.Cl Biol. Cell Mol. Rev. Nat. 21) evn h e fE tubules. ER of web the Weaving (2011). Nature 140 495-499. , 1205-1208. , a.Rv o.Cl Biol. Cell Mol. Rev. Nat. a.Rv o.Cl Biol. Cell Mol. Rev. Nat. ESLett. FEBS 28 601-605. , a.Cl Biol. Cell Nat. 2272-2282. , 21) ebaecrauein curvature Membrane (2010). 438 20) o synaptotagmin How (2007). 21) ig ntedistal the in hinge A (2010). 590-596. , 19) omto fcell of Formation (1992). a.Rv o.Cl Biol. Cell Mol. Rev. Nat. 21) ii elbiology. cell Lipid (2014). 19) esrdeffects Measured (1996). 22 555 430-436. , 12 u.Bohs J. Biophys. Eur. 62-65. , 127-138. , 16 14 .Cl Sci. Cell J. ur pn Cell Opin. Curr. 415-424. , 98-112. , 11 12 556-566. , 9 543-556. , 517-533. , Biochim. (2014). (2010). (2009). (2008). .Biol. J. Nature 1069 125 Nat. 21 1 , , ,

Journal of Cell Science aauti .S,Lcyr . tn,H .adLsc,R. Losick, and A. H. Stone, S., Lecuyer, S., K. Ramamurthi, F. W. Marshall, and M. S. Rafelski, osa,J . ig . ee,G .adLm,R A. R. Lamb, and P. G. Leser, X., Jing, S., J. Rossman, A. R. Lamb, and S. J. Rossman, Ro B. Baum, and L. J. Rohn, T. H. McMahon, and J. G. Praefcke, a,Y n ace V. Haucke, and Y. Rao, Lo R., L. Poulsen, GLANCE A AT SCIENCE CELL 1070 Martens, and I. Ibiricu, B., Zens, J., Romanov, C., Abert, J., Sawa-Makarska, Tuck, and L. J. Bessereau, K., M. Larsen, F., Richard, L., Nilsson, F., A. Ruaud, e,W,Brad . hmo,V,Gu,K,Wnshel . ez,D., Tenza, B., Windschiegl, K., Gaus, V., Chambon, L., Berland, W., mer, ¨ ellrarchitecture. cellular elDv Biol. Dev. Cell al. cells. into et uptake D. its Perrais, for C., invaginations J. 670-675. membrane Florent, V., tubular Fraisier, induces R., M. Aly, Sci. Cell J. bacterium. a in localization protein for cue molecules? fission and tubulation membrane S. endocytosis. and S. scission. membrane ESCRT-independent mediates protein superfamily. protein domain (BAR) answers. than questions more still 20) h .eeasP-TaeTT1rgltslssm biogenesis lysosome regulates TAT-1 P4-ATPase elegans C. The (2009). 21) ag idn oAg9umssadtoa t8bnigststo sites binding Atg8 additional unmasks Atg19 to binding Cargo (2014). 123 29 155-158. , pez-Marque ´ 551-569. , Traffic a.Rv o.Cl Biol. Cell Mol. Rev. Nat. 21) ebaesaigb h Bin/amphiphysin/Rvs the by shaping Membrane (2011). 10 21) ci n ellracietr taglance. a at architecture cellular and Actin (2010). 88-100. , s .L n amrn .G. M. Palmgren, and L. R. ´s, 21) ia ebaescission. membrane Viral (2013). 20) uligtecl:dsg rnilsof principles design cell: the Building (2008). el o.Lf Sci. Life Mol. Cell. el o.Lf Sci. Life Mol. Cell. 20) h yai uefml:universal superfamily: dynamin The (2004). Science a.Rv o.Cl Biol. Cell Mol. Rev. Nat. 9 593-602. , 323 21) nlez iu M2 virus Influenza (2010). 65 68 1354-1357. , 3119-3125. , 3983-3993. , 20) hg toxin Shiga (2007). Cell 20) Flippases: (2008). 20) Geometric (2009). 142 Nature nu Rev. Annu. 5 902-913. , 133-147. , 450 , tcoik .C,Shi,E . yn .J,An .S,Ssk,D Y., D. Sasaki, S., H. Ann, J., N. C. Unwin, Ryan, M., E. D. Schmid, Eliezer, C., and J. S. Stachowiak, J. Dittman, T., R. Wragg, D., Snead, aet,G,Phj,K . tdr . hm .adShka,R. Schekman, and S. Shim, S., Studer, B., K. Pahuja, G., Zanetti, R. Gautier, and B. Antonny, H., Barelli, H., Hirose, S., Vanni, hbt,Y,H,J,Kzo,M .adRppr,T A. T. Rapoport, and M. M. Kozlov, J., Hu, Y., Shibata, P. M. Sheetz, imreg .adKzo,M M. M. Kozlov, and J. Zimmerberg, Y. X. Ding, and G. T. Pomorski, Q., Xu, Y., R. Hu, S., Hanisch, J., Okkeri, P., Xu, hra,M . eslr .L,Fece,D .adHye,C C. C. Hayden, and A. D. crowding. Fletcher, protein-protein by L., P. bending Geissler, Membrane B., M. Sherman, complexin. of domain C-terminal the 4955. by sensing curvature 329-354. hpn h ebae fclua organelles. cellular of membranes the shaping Biol. Cell Mol. autophagy. selective 16 during apposition membrane-cargo mediate ebaecurvature. mammals. membrane highly in sorting member protein of family regulation the P4-ATPase and mouse novel a spermatogenesis. during of expressed Identification lipid modulate (2009). composition and recruitment. curvature protein membrane and how packing of view nanometre resolution. 425-433. , ora fCl cec 21)18 0517 doi:10.1242/jcs.114454 1065–1070 128, (2015) Science Cell of Journal 20) eie tutr ftenctncaeycoiercpo t4A at receptor acetylcholine nicotinic the of structure Refined (2005). .Ml Biol. Mol. J. 20) elcnrlb ebaectseeo adhesion. membrane-cytoskeleton by control Cell (2001). 2 392-396. , a.Rv o.Cl Biol. Cell Mol. Rev. Nat. 346 967-989. , a.Commun. Nat. .Cl Sci. Cell J. 20) o rtispouecellular produce proteins How (2006). 7 nu e.Cl e.Biol. Dev. Cell Rev. Annu. 122 9-19. , 5 a.Cl Biol. Cell Nat. 4916. , a.Cl Biol. Cell Nat. 2866-2876. , 20) Mechanisms (2009). 21) Membrane (2014). a.Commun. Nat. 14 21) sub- A (2014). 14 21) COPII (2012). a.Cl Biol. Cell Nat. 944-949. , 20-28. , a.Rev. Nat. (2012). 25 5 , ,

Journal of Cell Science