Phosphoinositide binding by the SNX27 FERM domain regulates localisation at the immune synapse of activated T-cells
0301 basic medicine
572
Immunological Synapses
T-Lymphocytes
Endosomes
Phosphoinositide
Lymphocyte Activation
1307 Cell Biology
Jurkat Cells
Mice
03 medical and health sciences
Phosphatidylinositol Phosphates
Cell Line, Tumor
Endosome
Animals
Humans
Amino Acid Sequence
Sorting Nexins
Immunological synapse
Binding Sites
Phox homology (PX) domain
Cell Membrane
4.1/ezrin/Radixin/moesin (FERM) domain
Protein Structure, Tertiary
Sorting nexin (SNX)
Protein Transport
Sequence Alignment
HeLa Cells
Protein Binding
Signal Transduction
DOI:
10.1242/jcs.158204
Publication Date:
2014-12-04T04:14:47Z
AUTHORS (8)
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.
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