uesad 02 Australia. 4072, Queensland, t oaiaina h muesnpeo ciae T-cells activated of Ghai synapse Rajesh immune regulates the domain at FERM localization SNX27 its the by binding Phosphoinositide ARTICLE RESEARCH eevd1 ue21;Acpe 4Nvme 2014 November 24 Accepted 2014; June 18 Received " ` cellular the for is superfamily 1 vital protein signals lipid-binding such spatio-temporal One specific homeostasis. domains lipid-binding elicit contain that they proteins and with system, collaboration endocytic biochemical and in secretory as the to act proteins of membrane organelles peripheral 2008; intracellular lipids various recruit Lemmon, These to serve 2006; 2010). that labels signal Camilli, al., De and et and Vanhaesebroeck trafficking Paolo membrane numerous (Di of transduction including regulation the to processes central are cellular that cues spatial as serve (PtdIns phospholipids Phosphatidylinositol INTRODUCTION Phosphoinositide synapse, Endosome, Immunological domain, domain, homology FERM Phox nexin, Sorting WORDS: KEY PtdIns new a phosphoinositide-lipid-binding discovered and the SNX27, full-length examined of we capabilities Here, the be clarified. to to remain translocation the localizes SNX27 underlying but mechanisms SNX27 manner, molecular activation-dependent T-cells, an In in synapse domain. immunological (PX) homology phox (PtdIns3 phosphatidylinositol-3-phosphate of binding mediated the is this which by endosomes to to SNX27 Crucial of recruitment cargos. the endosomal-to-cell-surface is protein function the transmembrane diverse controls of (SNX27) recycling 27 nexin Sorting ABSTRACT nvriyo e ot ae,Sde,NW utai,2052. Australia, NSW, The Sydney, Sciences, Wales, Biomolecular South and New Biotechnology of of University School The address: *Present Biotecnologı hshioiiednmc,adw idta etrigphosphoinositide perturbing that find we At and regulates dynamics, signaling approaches. phosphoinositide cell T-cells, activated modeling of and synapse and immunological bi- the mutagenesis for biophysical, preference clear through confirmed was a interaction the showed and phophoinositides, site tri-phosphorylated (FERM) binding moesin radixin, This ezrin, 4.1, domain. C-terminal the within site binding nbt nooa eyln oprmnsadPtdIns(3,4,5) and compartments distribution recycling SNX27 endosomal the alters both domain FERM in SNX27 the by binding o N2 rhsrto fcrotrafficking. cargo of orchestration SNX27 interactionsfor lipid unique partitioning of contribution the dynamic underscore and assembly, undergoes synapse immunological SNX27 during domains membrane different that between suggest results Our formation. synapse during membrane plasma the of domains enriched oa .Teasdale D. Rohan hs uhr otiue qal oti work this to equally contributed authors These nttt o oeua isine h nvriyo uesad t Lucia, St. Queensland, of University The Bioscience, Molecular for Institute uhr o orsodne([email protected];[email protected]) ([email protected]; correspondence for Authors 05 ulse yTeCmayo ilgssLd|Junlo elSine(05 2,5355doi:10.1242/jcs.158204 553–565 128, (2015) Science Cell of Journal | Ltd Biologists of Company The by Published 2015. ´ CB/SC -80,Mdi,Spain. Madrid, E-28409, (CNB)/CSIC, a 1, * , ` ai Tello-Lafoz Maria , 2 2 sblMe Isabel , ii inligLbrtr,Cnr ainlde Nacional Centro Laboratory, Signalling Lipid ´rida P 2, 2, )o phosphoinositides or s) ` " uan .Norwood J. Suzanne , n rt .Collins M. Brett and P )byits P P 3 - - yas Kys,20;Lfn ta. 00.Tesustained The 2000). al., et Lafont PtdInsP(3,4,5) of 2003; accumulation (Koyasu, synapse ru fteP uefml htcnanadfnn PtdIns defining a contain that superfamily PX the of group membranes. various decorate (PtdIns3 proteins phosphatidylinositol-3-phosphate with PX associating predominantly 2008; organelles, The secretory (Cullen, and 2012). endocytic m