Moesin-deficient mice reveal a non-redundant role for moesin in lymphocyte homeostasis

Abstract

Moesin is a member of the ezrin-radixin-moesin (ERM) family of cytoskeletal proteins. These proteins organize membrane domains by interacting with plasma membrane proteins and the actin cytoskeleton. Because of their high sequence similarity, ERM proteins are usually thought to be functionally redundant. Lymphocytes express two ERM proteins, ezrin and moesin. Whether each ERM plays a specialized role in lymphocytes, particularly in vivo, remains unknown. Here, we show that moesin has a crucial, non-redundant role in lymphocyte homeostasis. Moesin-deficient mice exhibited decreases in both T and B cells in the peripheral blood and lymph nodes, but not in the spleen. This phenotype was recapitulated in bone marrow (BM) chimeras with a hematopoietic moesin deficiency. Although the T and B cells apparently developed without major defects in the moesin-deficient mice, T cell egress from the thymus and immature B cell egress from the BM were impaired. In the periphery, both T and B cells showed delayed egress from lymphoid organs. We showed that moesin is the primary phosphorylated ERM subject to dynamic regulation during cell shape changes and migration. Our findings identify a previously unknown, non-redundant function of moesin in lymphocyte homeostasis in regulating lymphocyte egress from lymphoid organs.

Ezrin/radixin/moesin proteins differentially regulate endothelial hyperpermeability after thrombin

“…Moreover, ezrin, but not moesin, is phosphorylated on tyrosine in EGF-challenged human A431 cells despite tyrosine 145 conservation in both proteins (17). In addition, moesin has a nonredundant function in lymphocyte homeostasis (26). Our recent findings also support the distinct biological roles of these proteins in agonist-mediated EC barrier responses (1).…”

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

“…15,49,50) Vil2 KD/KD mice, on the other hand, can reach maturity, although they exhibited growth retardation, achlorhydria, 53) hypophosphatemia, osteomalacia, 55) and intrahepatic cholestasis. 56) These results suggest that only a small amount of ezrin is sufficient for their survival, but not for each physiological reaction in gastric parietal cells, renal proximal tubule cells, and intrahepatic cholangiocytes.…”

Membrane-organizing protein moesin controls Treg differentiation and antitumor immunity via TGF-β signaling

“…ERM proteins exist in 2 states: a closed/inactive state in which the FERM domain is tightly bound to the tail domain, masking the binding sites for other molecules; and a phosphorylated active/opened form that tethers between actin and receptors on the plasma membrane (1). Moesin is upregulated in multiple human cancers, including breast cancers (2), prostate (3), pancreatic (4), and lung and melanoma (5), and it is the dominant ERM protein in lymphocytes (6), where it has been implicated in the egress of T and B cells from the secondary lymphoid organs (7). No roles for moesin in CD4 + T cell specification have been defined.…”