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Publication : Conformational switching in ezrin regulates morphological and cytoskeletal changes required for B cell chemotaxis.

First Author  Parameswaran N Year  2011
Journal  J Immunol Volume  186
Issue  7 Pages  4088-97
PubMed ID  21339367 Mgi Jnum  J:170843
Mgi Id  MGI:4947472 Doi  10.4049/jimmunol.1001139
Citation  Parameswaran N, et al. (2011) Conformational switching in ezrin regulates morphological and cytoskeletal changes required for B cell chemotaxis. J Immunol 186(7):4088-97
abstractText  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.
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