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
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (62)
CITATIONS (20)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....