ArticleThe Journal of membrane biology2012
Cytoplasmic amino acids within the membrane interface region influence connexin oligomerization.
Article in The Journal of membrane biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Cx31.1 can selectively intermix with co-expressed connexins to facilitate its assembly into gap junctions.Journal of cell science · 2024Article
- Functional Consequences of Pathogenic Variants of theBiomolecules · 2023Review
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Role of Connexin 43 phosphorylation on Serine-368 by PKC in cardiac function and disease.Frontiers in cardiovascular medicine · 2022Review
- Polydisperse molecular architecture of connexin 26/30 heteromeric hemichannels revealed by atomic force microscopy imaging.The Journal of biological chemistry · 2020Article
- Connexin/Innexin Channels in Cytoplasmic Organelles. Are There Intracellular Gap Junctions? A Hypothesis!International journal of molecular sciences · 2020Article
- Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease.International journal of molecular sciences · 2018Review
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- A structural and functional comparison of gap junction channels composed of connexins and innexins.Developmental neurobiology · 2017Review
- Cardiac Cx43, Cx40 and Cx45 co-assembling: involvement of connexins epitopes in formation of hemichannels and Gap junction channels.BMC cell biology · 2017Review
- Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability.Circulation research · 2017Review
- Syndromic deafness mutations at Asn 14 differentially alter the open stability of Cx26 hemichannels.The Journal of general physiology · 2016Article
- Structural Studies of the Nedd4 WW Domains and Their Selectivity for the Connexin43 (Cx43) Carboxyl Terminus.The Journal of biological chemistry · 2016Article
- Targeting endothelial connexin40 inhibits tumor growth by reducing angiogenesis and improving vessel perfusion.Oncotarget · 2016Article
- Connexin Type and Fluorescent Protein Fusion Tag Determine Structural Stability of Gap Junction Plaques.The Journal of biological chemistry · 2015Article
- Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in Gap Junction Channels Composed of Connexin32.The Journal of biological chemistry · 2015Article
- Degradation of gap junction connexins is regulated by the interaction with Cx43-interacting protein of 75 kDa (CIP75).The Biochemical journal · 2015Article
- Structural determinants and proliferative consequences of connexin 37 hemichannel function in insulinoma cells.The Journal of biological chemistry · 2014Article
- Characterization of the connexin45 carboxyl-terminal domain structure and interactions with molecular partners.Biophysical journal · 2014Article
- Mix and match: investigating heteromeric and heterotypic gap junction channels in model systems and native tissues.FEBS letters · 2014Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Gap junction channels composed of connexins connect cells, allowing intercellular communication. Their cellular assembly involves a unique quality-control pathway. Some connexins [including connexin43 (Cx43) and Cx46] oligomerize in the trans-Golgi network following export of stabilized monomers from the endoplasmic reticulum (ER). In contrast, other connexins (e.g., Cx32) oligomerize early in the secretory pathway. Amino acids near the cytoplasmic aspect of the third transmembrane domain have previously been shown to determine this difference in assembly sites. Here, we characterized the oligomerization of two connexins expressed prominently in the vasculature, Cx37 and Cx40, using constructs containing a C-terminal dilysine-based ER retention/retrieval signal (HKKSL) or treatment with brefeldin A to block ER vesicle trafficking. Both methods led to intracellular retention of connexins, since the cells lacked gap junction plaques. Retention of Cx40 in the ER prevented it from oligomerizing, comparable to Cx43. By contrast, ER-retained Cx37 was partially oligomerized. Replacement of two amino acids near the third transmembrane domain of Cx43 (L152 and R153) with the corresponding amino acids from Cx37 (M152 and G153) resulted in early oligomerization in the ER. Thus, residues that allow Cx37 to oligomerize early in the secretory pathway could restrict its interactions with coexpressed Cx40 or Cx43 by favoring homomeric oligomerization, providing a structural basis for cells to produce gap junction channels with different connexin composition.
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