Moesin Controls Clathrin-Mediated S1PR1 Internalization in T Cells

• DOI: 10.1371/journal.pone.0082590
• Publication Date: 2013-12-16T16:39:15Z
• Authors: Akira Nomachi; Masanori Yoshinaga; Jaron Liu; Pakorn Kanchanawong; Kiyoshi Tohyama; Dean Thumkeo; Takeshi Watanabe; Shuh Narumiya; Takako Hirata
• Keywords: Internalization; Moesin; S1PR1; Radixin

The lipid mediator sphingosine 1-phosphate (S1P) regulates a wide range of cellular activities, including vascular maturation, angiogenesis, and immune-cell trafficking. Among the five known receptors for S1P (S1PR1-S1PR5), S1PR1 is critical regulator lymphocyte trafficking: its signaling required egress from lymphoid organs, while down-modulation by agonist-induced internalization prerequisite entry into organs bloodstream. Despite importance down-regulation in determining behavior, molecular mechanism lymphocytes has not been defined. Here we show that T cells occurs via clathrin-mediated endocytosis regulated moesin, an ezrin-radixin-moesin (ERM) family member. In S1P-stimulated cells, relocalized within clathrin-coated vesicles (CCVs) early endosomes, was blocked when clathrin pharmacologically inhibited. Stimulating moesin-deficient with failed to induce CCV formation. Furthermore, treating mice FTY720, receptor agonist internalize S1PR1, caused delayed lymphopenia, isolated FTY720-treated still responded ex vivo chemotaxis assays. These results reveal novel role moesin regulating clathrin-dependent through