ArticleMolecular biology of the cell2013
Two tyrosine-based sorting signals in the Cx43 C-terminus cooperate to mediate gap junction endocytosis.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- The relationship between Connexin 43 (Cx43) and partner protein, human discs large homologue-1 (Dlg1) during wound closure in keratinocytes.Cell and tissue research · 2026Article
- Cx45 regulation by kinases and impact of expression in heart failure.Journal of molecular and cellular cardiology · 2025Article
- Connexin43 promotes exocytosis of damaged lysosomes through actin remodelling.The EMBO journal · 2024Article
- The E3 ubiquitin ligase ITCH negatively regulates intercellular communication via gap junctions by targeting connexin43 for lysosomal degradation.Cellular and molecular life sciences : CMLS · 2024Article
- Endocytosis and Endocytic Motifs across the Connexin Gene Family.International journal of molecular sciences · 2023Article
- Regulation of Cx43 Gap Junction Intercellular Communication by Bruton's Tyrosine Kinase and Interleukin-2-Inducible T-Cell Kinase.Biomolecules · 2023Article
- The roles of connexins and gap junctions in the progression of cancer.Cell communication and signaling : CCS · 2023Review
- Role of Connexin 43 phosphorylation on Serine-368 by PKC in cardiac function and disease.Frontiers in cardiovascular medicine · 2022Review
- Impaired Cx43 gap junction endocytosis causes morphological and functional defects in zebrafish.Molecular biology of the cell · 2021Article
- Myocardial infarction affects Cx43 content of extracellular vesicles secreted by cardiomyocytes.Life science alliance · 2020Article
- Src Regulation of Cx43 Phosphorylation and Gap Junction Turnover.Biomolecules · 2020Article
- Endocytosis of BRASSINOSTEROID INSENSITIVE1 Is Partly Driven by a Canonical Tyr-Based Motif.The Plant cell · 2020Article
- Article
- Connexin 43 gap junctional intercellular communication inhibitsDevelopment (Cambridge, England) · 2020Article
- A Conserved LIR Motif in Connexins Mediates Ubiquitin-Independent Binding to LC3/GABARAP Proteins.Cells · 2020Article
- Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications.Cellular and molecular life sciences : CMLS · 2020Review
- Endocytic Adaptor Proteins in Health and Disease: Lessons from Model Organisms and Human Mutations.Cells · 2019Review
- Connexin-43 K63-polyubiquitylation on lysines 264 and 303 regulates gap junction internalization.Journal of cell science · 2018Article
- Loss of Cx43-Mediated Functional Gap Junction Communication in Meningeal Fibroblasts Following Mouse Hepatitis Virus Infection.Molecular neurobiology · 2018Article
- Protein⁻Protein Interactions with Connexin 43: Regulation and Function.International journal of molecular sciences · 2018Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Gap junction (GJ) channels that electrically and chemically couple neighboring cells are formed when two hemichannels (connexons) of apposed cells dock head-on in the extracellular space. Remarkably, docked connexons are inseparable under physiological conditions, and we and others have shown that GJs are internalized in whole, utilizing the endocytic clathrin machinery. Endocytosis generates double-membrane vesicles (annular GJs or connexosomes) in the cytoplasm of one of the apposed cells that are degraded by autophagosomal and, potentially, endo/lysosomal pathways. In this study, we investigated the structural motifs that mediate Cx43 GJ endocytosis. We identified three canonical tyrosine-based sorting signals of the type "YXXΦ" in the Cx43 C-terminus, two of which function cooperatively as AP-2 binding sites. We generated a set of green fluorescent protein-tagged and untagged Cx43 mutants that targeted these two sites either individually or together. Mutating both sites completely abolished Cx43-AP-2/Dab2/clathrin interaction and resulted in increased GJ plaque size, longer Cx43 protein half-lives, and impaired GJ internalization. Interestingly, Dab2, an accessory clathrin adaptor found earlier to be important for GJ endocytosis, interacts indirectly with Cx43 via AP-2, permitting the recruitment of up to four clathrin complexes per Cx43 protein. Our analyses provide a mechanistic model for clathrin's efficient internalization of large plasma membrane structures, such as GJs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.