Journal of Cell Science o:10.1242/jcs.120840 doi: 4589–4601 126, Science Cell of Journal 2013 July 17 Accepted raiainadatcmn fmcouue othe to cortex microtubules cell of attachment dynamics, and regulates and organization CLASP2 to binds 4.1R Protein Article Research einkona h FR oan Cihie l,19)that 1998) al., et (Chishti conserved domain’ highly ‘FERM a the contain as members known whose region of all superfamily, mechanisms molecular the platforms. determine cortical to organizing is in research aim involved major of A field 2005). this al., 2001; et in al., MT Mimori-Kiyosue 2006; et asymmetric al., (Akhmanova et migration regulating Lansbergen and thereby polarity cell and organization, attachment, MT ensuring and platforms, bridging cortical a capture and as ends acts distal CLASP2 MT 2006). between al., protein et proteins (Lansbergen cortex cell non-MT-binding the contain these LL5 also of as such function which major A platforms, platforms, dynamics edge. cells, leading motile ‘peripheral’ cortical the in at or and, enriched MT membrane strongly plasma ‘cortical’ are 2010). the of near protein-2 regulate located (Galjart, part are linker-associated which structures also and cytoplasmic other are including (CLASP2), with plus-ends +TIPs, MTs Some of MT interactions and growing bind (+TIPs) diverse proteins to A plus-end-tracking MT 1984). called and Kirschner, proteins known of and polymerization group behavior (Mitchison a instability of dynamic 2003), phases as Hyman, and between (Howard polarized switch depolymerization are MTs cellular that migration. many and filaments for polarity essential cell including is functions cytoskeleton (MT) microtubule The Introduction Our distribution. polarity. cell radial for their essential losing dynamics cortical and CLASP2 and margins behavior, organization words: cell CLASP2 MT Key controlling at correct locally bending in enabling grow, 4.1R locally activity, protein to by GSK3 but scaffolding continued edge edges, the and correct cell cell MTs for turnover of the the role cortex, vicinity platform at unidentified for the cell MTs previously in required the a to longer is for suggest to CLASP2 maintained results of and tethered were we binding plus-ends being CLASP2 Here controls MT detail. of cortical cells also in 4.1R-knockdown instead 4.1R with described in Protein been colocalizes Furthermore, platforms. yet activity. and cortical GSK3 not altering CLASP2 have interacts of platforms protein, these LL5 dynamics platforms, FERM-domain-containing as organizing and Cortical such in number a migration. proteins involved binding 4.1R, and mechanisms non-MT the polarity that and However, cell CLASP2, show cortex. as including cell such processes, the proteins, plus-end-tracking cellular to MT MTs many of for subset a essential by is formed cytoskeleton (MT) microtubule The Summary work this to equally ` contributed authors *These 3 2 1 Ruiz-Saenz Ana nvria Auto Universidad iulA Alonso A. Miguel uhr o orsodne( correspondence for Authors rtoisCne,EamsMdclCne,31 ERtedm h Netherlands The Netherlands Rotterdam, The GE Rotterdam, 3015 GE Center, 3015 Medical Center, Erasmus Medical Center, Erasmus Proteomics Biology, Cell of Department Biologı de Centro 03 ulse yTeCmayo ilgssLtd Biologists of Company The by Published 2013. rti .Ri h onigmme ftelrebn 4.1 band large the of member founding the is 4.1R Protein b irtbl yais rti .R LS2 otclpafrs irtbl organization Microtubule platforms, Cortical CLASP2, 4.1R, Protein dynamics, Microtubule n LS(lokona R1,i oatc T to MTs attach to is ERC1), as known (also ELKS and nm eMdi CI n A) Nicola UAM), and (CSIC Madrid de ´noma aMlclrSvr co n eatmnod Biologı de Departamento and Ochoa Severo Molecular ´a 1 efe a Haren van Jeffrey , 1 il Galjart Niels , [email protected] 2, ; * [email protected] , ` 2 n sblCorreas Isabel and .LuaSayas Laura C. , sCbea1 84 ard Spain Madrid, 28049 1, Cabrera ´s ) 1 ar Rangel Laura , 1, aMlclr osj ueird netgcoe Cientı Investigaciones de Superior Consejo Molecular, ´a * nadto,arl o .Ra ikrbtenteactin the between linker a as 2011). (Mattagajasingh 4.1R junctions al., tight for of et 2002) components role and al., a (Meyer cytoskeleton et addition, 4.1R machinery (Krauss association that assembly In splicing centrosome–nucleus nuclear determined proper the analyses and for Further nuclear of essential 1998). organizing is components al., in et interactions and 4.1R (Lallena showing for 4.1R studies role from between A established was 1999). architecture al., et (Luque the Pe including Pe sites 1997; subcellular Ca multiple (de 4.1R nucleus at protein 1990). cells, the localize nucleated al., of in isoforms et splicing that, Tang showed alternative studies 1999; extensive these Subsequent al., (Conboy, in the 4.1R et to pre-mRNA of due 4.1R-encoding (Anderson pattern mainly expression 4.1R cells is complex protein cells the nucleated that of and that isoforms 1988) It however, 1993). multiple (Conboy, discovered, express lipids subsequently interactions and underlying 80-kDa through proteins was the bilayer membrane of lipid an integral attachment overlying spectrin– with the the the as to stabilizes mediates 4.1R cytoskeleton and protein identified network red cells, human these actin of originally In skeleton cells. membrane blood the was of protein 2001). multifunctional 4.1R Baines, and (Bennett lipids Protein and proteins membrane binds , ` ´ e-erioe l,20)adteedpamcreticulum endoplasmic the and 2001) al., et rez-Ferreiro ´ e-erioe l,20) T Hage l,2004; al., et (Huang MTs 2004), al., et rez-Ferreiro ´ 1 cre l,19) h etooe(ruse al., et (Krauss centrosome the 1995), al., et rcer eonDemmers Jeroen , 3 am Milla Jaime , b tahdsa nsof ends distal attach , fcsand ´ficas ´n 1 , 4589 Journal of Cell Science rti .Ri salsigM ewr smer tthe at and polarity. organization asymmetry cell MT scaffolding for radial network correct essential the the their MT dynamics ensuring of thereby losing establishing role edge, and in key leading a margins 4.1R suggest grow, cell protein results to at Our continue but curling distribution. properly, and captured not bending the approach are that CLASP2 MTs periphery growing of of and cell by association increases, reduction lattice the MT upon plus-ends that polarity, the and result, with lose MT indicate a cells dynamics data to As expression, activity. 4.1R Our binding organization, GSK3 cortex. 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J. Bulinski, and G. G. Gundersen, N. Galjart, ten-anvle .adHl,A. Hall, and S. Etienne-Manneville, ree,S,Frer,R,vnZn . tobui,J,Jel,M,Govl,F., Grosveld, M., Jaegle, J., Strouboulis, A., Zon, van R., Ferreira, S., Driegen, Sayas, R., Horssen, van K., Draegestein, T., Stepanova, M., Ham, van K., Drabek, rus .W,Cai,J . oes . oads . rcmli,G and G. Krockmalnic, N., Mohandas, C., Rogers, A., J. Chasis, W., S. Krauss, eCa de Cordelie M., Caspi, M., F. Coquelle, otoiniKntnools . un,S .adBn,E . Jr J., E. Benz, and C. S. Huang, A., Kontrogianni-Konstantopoulos, ora,I,Lt,T . pihr .W n acei .T. V. Marchesi, and W. D. Speicher, L., T. Leto, I., Correas, oaoa .A,Ahaoa .S,Kjm,S,Glat .adBrs,G G. G. Borisy, and N. Galjart, S., Kojima, S., A. Akhmanova, A., Y. Komarova, oby J. Conboy, ug .Y,Tn,C .adTn,T K. T. Tang, and J. C. Tang, Y., L. Hung, Jr J., E. Benz, and S. E. Liu, R., Jagadeeswaran, C., S. Huang, hst,A . i,A . afta .M,Ltha,M,Hnpl . idl H., Jindal, M., Hanspal, M., Lutchman, M., S. 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