Early Endosomes Undergo Calcium-Triggered Exocytosis and Enable Repair of Diffuse and Focal Plasma Membrane Injury
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
calcium; early endosomes; endocytosis; exocytosis; pore forming toxins; wounds
Cells are routinely exposed to agents that cause plasma membrane (PM) injury. While pore-forming toxins (PFTs), and chemicals cause nanoscale holes dispersed throughout the PM, mechanical trauma causes focal lesions in the PM. To examine if these distinct injuries share common repair mechanism, membrane trafficking is monitored as the PM repairs from such injuries. During the course of repair, dispersed PM injury by the PFT Streptolysin O activates endocytosis, while focal mechanical injury to the PM inhibits endocytosis. Consequently, acute block of endocytosis prevents repair of diffuse, but not of focal injury. In contrast, a chronic block in endocytosis depletes cells of early endosomes and inhibits repair of focal injury. This study finds that both focal and diffuse PM injury activate Ca -triggered exocytosis of early endosomes. The use of markers including endocytosed cargo, Rab5, Rab11, and VAMP3, all reveal injury-triggered exocytosis of early endosomes. Inhibiting Rab5 prevents injury-triggered early endosome exocytosis and phenocopies the failed PM repair of cells chronically depleted of early endosomes. These results identify early endosomes as a Ca -regulated exocytic compartment, and uncover the requirement of their dual functions - endocytosis and regulated exocytosis, to differentially support PM repair based on the nature of the injury.
Bittel, Daniel C. and Jaiswal, Jyoti K., "Early Endosomes Undergo Calcium-Triggered Exocytosis and Enable Repair of Diffuse and Focal Plasma Membrane Injury" (2023). GW Authored Works. Paper 3413.
Genomics and Precision Medicine