title: Conformational switching in ezrin regulates morphological and cytoskeletal changes required for B cell chemotaxis.
abstract: B cell chemotaxis occurs in response to specific chemokine gradients and is critical for homeostasis and immune response. The molecular regulation of B cell membrane-actin interactions during migration is poorly understood. In this study, we report a role for ezrin, a member of the membrane-cytoskeleton cross-linking ezrin-radixin-moesin proteins, in the regulation of the earliest steps of B cell polarization and chemotaxis. We visualized chemokine-induced changes in murine B cell morphology using scanning electron microscopy and spatiotemporal dynamics of ezrin in B cells using epifluorescence and total internal reflection microscopy. Upon chemokine stimulation, ezrin is transiently dephosphorylated to assume an inactive conformation and localizes to the lamellipodia. B cells expressing a phosphomimetic conformationally active mutant of ezrin or those in which ezrin dephosphorylation was pharmacologically inhibited displayed impaired microvillar dynamics, morphological polarization, and chemotaxis. Our data suggest a 2-fold involvement of ezrin in B cell migration, whereby it first undergoes chemokine-induced dephosphorylation to facilitate membrane flexibility, followed by relocalization to the actin-rich lamellipodia for dynamic forward protrusion of the cells.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Neetha
authors.initials: N
authors.lastname: Parameswaran
authors.forename: Ken
authors.initials: K
authors.lastname: Matsui
authors.forename: Neetu
authors.initials: N
authors.lastname: Gupta
mesh_terms: D000199:Actins / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics*; D003599:Cytoskeleton / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D011487:Protein Conformation; D011554:Pseudopodia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D013912:Threonine / Q000737:chemistry / Q000235:genetics; D000099149:Ezrin
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D013912:Threonine; D000099149:Ezrin; C071058:moesin