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https://hdl.handle.net/10316/116153
Title: | Connexin43 promotes exocytosis of damaged lysosomes through actin remodelling | Authors: | Domingues, Neuza S. Catarino, Steve Cristóvão, Beatriz Rodrigues, Lisa Carvalho, Filomena A Sarmento, Maria João Zuzarte, Mónica Almeida, Jani-Sofia Ribeiro-Rodrigues, Teresa Correia-Rodrigues, Ânia Fernandes, Fábio Rodrigues-Santos, Paulo Aasen, Trond Santos, Nuno C Korolchuk, Viktor I Gonçalves, Teresa M. Milosevic, Ira Raimundo, Nuno Girão, Henrique |
Keywords: | Actin-remodelling; Arp2; Connexin43; Exocytosis; Lysosomal Damage | Issue Date: | 23-Jul-2024 | Project: | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04539/2020 info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP/04539/2020 PTDC/MED-NEU/8030/2020 |
Serial title, monograph or event: | The EMBO Journal | Abstract: | A robust and efficient cellular response to lysosomal membrane damage prevents leakage from the lysosome lumen into the cytoplasm. This response is understood to happen through either lysosomal membrane repair or lysophagy. Here we report exocytosis as a third response mechanism to lysosomal damage, which is further potentiated when membrane repair or lysosomal degradation mechanisms are impaired. We show that Connexin43 (Cx43), a protein canonically associated with gap junctions, is recruited from the plasma membrane to damaged lysosomes, promoting their secretion and accelerating cell recovery. The effects of Cx43 on lysosome exocytosis are mediated by a reorganization of the actin cytoskeleton that increases plasma membrane fluidity and decreases cell stiffness. Furthermore, we demonstrate that Cx43 interacts with the actin nucleator Arp2, the activity of which was shown to be necessary for Cx43-mediated actin rearrangement and lysosomal exocytosis following damage. These results define a novel mechanism of lysosomal quality control whereby Cx43-mediated actin remodelling potentiates the secretion of damaged lysosomes. | URI: | https://hdl.handle.net/10316/116153 | ISSN: | 1460-2075 | DOI: | 10.1038/s44318-024-00177-3 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais |
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domingues-et-al-2024-connexin43-promotes-exocytosis-of-damaged-lysosomes-through-actin-remodelling.pdf | 6.87 MB | Adobe PDF | View/Open |
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