title: 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.
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan. thirata@ak.med.kyoto-u.ac.jp
authors.forename: Takako
authors.initials: T
authors.lastname: Hirata
authors.forename: Akira
authors.initials: A
authors.lastname: Nomachi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tohya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D002465:Cell Movement / Q000276:immunology; D048430:Cell Shape / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006706:Homeostasis / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008855:Microscopy, Electron, Scanning; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin