Sequential binding of ezrin and moesin to L-selectin regulates monocyte protrusive behaviour during transendothelial migration.

Journal of Cell Science
Angela Rey-GallardoAleksandar Ivetic

Abstract

Leukocyte transendothelial migration (TEM) is absolutely fundamental to the inflammatory response, and involves initial pseudopod protrusion and subsequent polarised migration across inflamed endothelium. Ezrin/radixin/moesin (ERM) proteins are expressed in leukocytes and mediate cell shape changes and polarity. The spatio-temporal organisation of ERM proteins with their targets, and their individual contribution to protrusion during TEM, has never been explored. Here, we show that blocking binding of moesin to phosphatidylinositol 4,5-bisphosphate (PIP2) reduces its C-terminal phosphorylation during monocyte TEM, and that on-off cycling of ERM activity is essential for pseudopod protrusion into the subendothelial space. Reactivation of ERM proteins within transmigrated pseudopods re-establishes their binding to targets, such as L-selectin. Knockdown of ezrin, but not moesin, severely impaired the recruitment of monocytes to activated endothelial monolayers under flow, suggesting that this protein plays a unique role in the early recruitment process. Ezrin binds preferentially to L-selectin in resting cells and during early TEM. The moesin-L-selectin interaction increases within transmigrated pseudopods as TEM proceeds, facilit...Continue Reading

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Citations

Jun 14, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Louisa YeungMichael J Hickey
Feb 27, 2020·International Journal of Molecular Sciences·Almudena García-Ortiz, Juan Manuel Serrador
May 30, 2019·Frontiers in Immunology·Aleksandar IveticSamuel James Hart
Jan 8, 2021·Journal of Cell Science·Izajur RahmanAleksandar Ivetic
Apr 15, 2020·The American Journal of Pathology·Yuhua XueGeorge K Michalopoulos
Jun 11, 2021·Frontiers in Immunology·Vanessa ChilundaJoan W Berman

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Methods Mentioned

BETA
confocal microscopy
fluorescence
FRET
PMA
flow cytometry
FCS
PCR

Software Mentioned

TRI2
COR Image Studio
LI
Volocity

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