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

• DOI: 10.1242/jcs.158204
• Publication Date: 2014-12-04T04:14:47Z
• Authors: Rajesh Ghai; Maria Tello-Lafoz; Suzanne J. Norwood; Zhe Yang; Thomas Clairfeuille; Rohan D. Teasdale; Isabel Mérida; Brett M. Collins
• Keywords: Immunological synapse

Sorting nexin 27 (SNX27) controls the endosomal to cell-surface recycling of diverse transmembrane protein cargos. Critical this function is recruitment SNX27 endosomes through binding phosphatidylinositol-3-phosphate (PtdIns3P) by phox-homology (PX) domain. In T cells, polarized immunological synapse (IS) in an activation-dependent manner, but molecular mechanisms underlying translocation remain be clarified. Here, we examined phosphoinositide lipid-binding capabilities full-length SNX27, and discovered a novel PtdInsP site within C-terminal 4.1/ezrin/radixin/moesin (FERM) This showed clear preference for di tri-phosphorylated phophoinositides, interaction was confirmed biophysical, mutagenesis modeling approaches. At IS activated T-cells cell signaling regulates dynamics, find that perturbing FERM domain alters its distribution both compartments PtdIns(3,4,5)P3-enriched domains plasma membrane during formation. Our results suggest undergoes dynamic partitioning between different assembly, underscore contribution unique lipid interactions orchestration cargo trafficking.