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PHOSPHATIDYLSERINE EXPOSURE AND EXTRACELLULAR ANNEXIN A5 WEAKEN THE ACTIN CORTEX IN OSTEOCLAST FUSION.


ABSTRACT: Diverse cell-cell fusions involve intracellular Ca2+ signaling, non-apoptotic exposure of phosphatidylserine (PS) at the surface of fusion-committed cells and binding of extracellular Annexin A5 (Anx A5). Here we focus on the cell fusion stage of formation of bone-resorbing multinucleated osteoclasts and report that each of the listed hallmarks of cell fusion represents a step in a novel bidirectional signaling pathway. A rise in intracellular Ca2+ activates a lipid scramblase that translocates PS from the inner to the outer leaflet of the plasma membrane. This redistribution is enhanced by extracellular Anx A5 binding to cell surface PS. Depletion of PS in the inner leaflet weakens actin cortex-plasma membrane attachment mediated by ezrin/radixin/moesin (ERM) proteins, as evide

SUBMITTER: Leikina E 

PROVIDER: S-EPMC12312182 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature