Should it stay or should it go: gap junction protein GJA1/Cx43 conveys damaged lysosomes to the cell periphery to potentiate exocytosis

GJA1/Cx43 (gap junction protein alpha 1) has long been associated with gap junctions-mediated communication between adjacent cells. However, recent data have defied this concept, with studies implicating GJA1 in other biological processes, such as macroautophagy/autophagy regulation, mitochondrial activity and extracellular vesicles biology. In our recent study we unveiled an additional role played by GJA1 in lysosomal trafficking. We demonstrate that GJA1 promotes the exocytosis of damaged lysosomes, through a mechanism that relies on ACTR2/ARP2-ACTR3/ARP3-dependent actin remodeling. Our findings ascribe to GJA1 an important role during pathogen infection and lysosomal storage disorders, favoring the release of dysfunctional lysosomes.

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Publication Details

Journal
Autophagy
Published
2024-10-12
DOI
https://doi.org/10.1080/15548627.2024.2408711
Primary Topic
Connexins and lens biology
Type
article
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article

Should it stay or should it go: gap junction protein GJA1/Cx43 conveys damaged lysosomes to the cell periphery to potentiate exocytosis

Neuza Domingues, Teresa Ribeiro‐Rodrigues, Henrique Girão
Autophagy
Connexins and lens biology
article

Should it stay or should it go: gap junction protein GJA1/Cx43 conveys damaged lysosomes to the cell periphery to potentiate exocytosis

Neuza Domingues, Teresa Ribeiro‐Rodrigues, Henrique Girão
article en

Abstract

GJA1/Cx43 (gap junction protein alpha 1) has long been associated with gap junctions-mediated communication between adjacent cells. However, recent data have defied this concept, with studies implicating GJA1 in other biological processes, such as macroautophagy/autophagy regulation, mitochondrial activity and extracellular vesicles biology. In our recent study we unveiled an additional role played by GJA1 in lysosomal trafficking. We demonstrate that GJA1 promotes the exocytosis of damaged lysosomes, through a mechanism that relies on ACTR2/ARP2-ACTR3/ARP3-dependent actin remodeling. Our findings ascribe to GJA1 an important role during pathogen infection and lysosomal storage disorders, favoring the release of dysfunctional lysosomes.

AutophagyVol. 20(12)
Escola Superior de Tecnologia da Saúde de Coimbra (PT), University of Coimbra (PT)
Zero hunger
Openalex Percentile: Top 84%
Connexins and lens biology
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