title: Constitutively active ezrin increases membrane tension, slows migration, and impedes endothelial transmigration of lymphocytes in vivo in mice.
abstract: ERM (ezrin, radixin moesin) proteins in lymphocytes link cortical actin to plasma membrane, which is regulated in part by ERM protein phosphorylation. To assess whether phosphorylation of ERM proteins regulates lymphocyte migration and membrane tension, we generated transgenic mice whose T-lymphocytes express low levels of ezrin phosphomimetic protein (T567E). In these mice, T-cell number in lymph nodes was reduced by 27%. Lymphocyte migration rate in vitro and in vivo in lymph nodes decreased by 18% to 47%. Lymphocyte membrane tension increased by 71%. Investigations of other possible underlying mechanisms revealed impaired chemokine-induced shape change/lamellipod extension and increased integrin-mediated adhesion. Notably, lymphocyte homing to lymph nodes was decreased by 30%. Unlike most described homing defects, there was not impaired rolling or sticking to lymph node vascular endothelium but rather decreased migration across that endothelium. Moreover, decreased numbers of transgenic T cells in efferent lymph suggested defective egress. These studies confirm the critical role of ERM dephosphorylation in regulating lymphocyte migration and transmigration. Of particular note, they identify phospho-ERM as the first described regulator of lymphocyte membrane tension, whose increase probably contributes to the multiple defects observed in the ezrin T567E transgenic mice.
authors: Experimental Immunology Branch, National Cancer Institute, Bethesda, MD, USA.
authors: Yin
authors: Y
authors: Liu
authors: Natalya V
authors: NV
authors: Belkina
authors: Chung
authors: C
authors: Park
authors: Raj
authors: R
authors: Nambiar
authors: Scott M
authors: SM
authors: Loughhead
authors: Genaro
authors: G
authors: Patino-Lopez
authors: Khadija
authors: K
authors: Ben-Aissa
authors: Jian-Jiang
authors: JJ
authors: Hao
authors: Michael J
authors: MJ
authors: Kruhlak
authors: Hai
authors: H
authors: Qi
authors: Ulrich H
authors: UH
authors: von Andrian
authors: John H
authors: JH
authors: Kehrl
authors: Matthew J
authors: MJ
authors: Tyska
authors: Stephen
authors: S
authors: Shaw
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D000099149:Ezrin