Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells

Ghai, Rajesh, Tello-Lafoz, Maria, Norwood, Suzanne J., Yang, Zhe, Clairefeuille, Thomas, Teasdale, Rohan D., Mérida, Isabel and Collins, Brett M. (2015) Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells. Journal of Cell Science, 128 3: 553-565. doi:10.1242/jcs.158204

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Author Ghai, Rajesh
Tello-Lafoz, Maria
Norwood, Suzanne J.
Yang, Zhe
Clairefeuille, Thomas
Teasdale, Rohan D.
Mérida, Isabel
Collins, Brett M.
Title Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 0021-9533
Publication date 2015-02-01
Year available 2014
Sub-type Article (original research)
DOI 10.1242/jcs.158204
Open Access Status File (Publisher version)
Volume 128
Issue 3
Start page 553
End page 565
Total pages 13
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Language eng
Subject 1307 Cell Biology
Abstract Sorting nexin 27 (SNX27) controls the endosomal to cell-surface recycling of diverse transmembrane protein cargos. Critical to this function is the recruitment of SNX27 to endosomes through the binding of phosphatidylinositol-3-phosphate (PtdIns3P) by the phox-homology (PX) domain. In T cells, SNX27 is polarized to the immunological synapse (IS) in an activation-dependent manner, but the molecular mechanisms underlying SNX27 translocation remain to be clarified. Here, we examined the phosphoinositide lipid-binding capabilities of full-length SNX27, and discovered a novel PtdInsP binding site within the C-terminal 4.1/ezrin/radixin/moesin (FERM) domain. This binding site showed a clear preference for di and tri-phosphorylated phophoinositides, and the interaction was confirmed through biophysical, mutagenesis and modeling approaches. At the IS of activated T-cells cell signaling regulates phosphoinositide dynamics, and we find that perturbing phosphoinositide binding by the SNX27 FERM domain alters its distribution in both endosomal recycling compartments and PtdIns(3,4,5)P3-enriched domains of the plasma membrane during synapse formation. Our results suggest that SNX27 undergoes dynamic partitioning between different membrane domains during IS assembly, and underscore the contribution of unique lipid interactions for SNX27 orchestration of cargo trafficking.
Keyword Sorting nexin (SNX)
Phox homology (PX) domain
4.1/ezrin/Radixin/moesin (FERM) domain
Immunological synapse
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP120103930
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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Created: Tue, 16 Dec 2014, 01:20:37 EST by Susan Allen on behalf of Institute for Molecular Bioscience