title: A role for novel lipid interactions in the dynamic recruitment of SNX27 to the T-cell immune synapse.
abstract: SNX27 is a member of the sorting nexin family that plays an important role in the recycling of receptors from endosomes to the cell surface. In addition to a PX (Phox homology) domain that regulates its endosomal localization, SNX27 has a unique PDZ (Psd-95/Dlg/ZO1) domain and an atypical FERM (4.1, ezrin, radixin, moesin) domain that both function to bind short peptide sequence motifs in the cytoplasmic domains of the cargo receptors. Using the T cell immune synapse (IS) as a model for polarized protein recycling, we recently identified an additional mechanism that enhances SNX27 localization to the endosomal recycling compartment (ERC). Our study defined a phosphoinositide (PI) lipid-binding site within the SNX27 FERM domain, with a clear preference for bi- and triphosphorylated PIs, which may promote SNX27 localization to phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) and/or PtdIns(3,4,5)P3-enriched membrane domains. Using fluorescently tagged lipid-binding probes, we studied the kinetics of distinct PIs in living T cells during IS formation. Our results suggest that PtdIns(3,4,5)P3 accumulates at the contact site simultaneously with early SNX27 recruitment to the plasma membrane (PM), and this is partly controlled by by lipid binding through the FERM domain. These studies define 2 independent binding sites for PtdIns-derived lipids in SNX27, that contribute to the dynamic recruitment of SNX27 to distinct membranes during T cell activation.
authors.affiliation: a Lipid Signaling Laboratory ; Centro Nacional de Biotecnología (CNB)/CSIC ; Madrid , Spain.
authors.forename: María
authors.initials: M
authors.lastname: Tello-Lafoz
authors.affiliation: b Institute for Molecular Bioscience ; The University of Queensland ; St. Lucia , Australia.|c Current address: The School of Biotechnology and Biomolecular Sciences , The University of New South Wales , Sydney , NSW , Australia.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ghai
authors.affiliation: b Institute for Molecular Bioscience ; The University of Queensland ; St. Lucia , Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Collins
authors.affiliation: a Lipid Signaling Laboratory ; Centro Nacional de Biotecnología (CNB)/CSIC ; Madrid , Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Mérida
mesh_terms: D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D008563:Membrane Lipids / Q000378:metabolism*; D054731:PDZ Domains; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D058305:Sorting Nexins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D008563:Membrane Lipids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; C522885:SNX27 protein, human; D058305:Sorting Nexins; C060974:phosphatidylinositol 3,4,5-triphosphate
keywords: 4.1/ezrin/Radixin/moesin (FERM) domain.; Diacylglicerol kinase (DGK); Psd-95/Dlg/ZO1 (PDZ) domain; Sorting nexin (SNX); T lymphocytes; endosome; immunological synapse; phosphoinositide; phox homology (PX) domain