ArticleMolecular biology of the cell2009
Conformational maturation and post-ER multisubunit assembly of gap junction proteins.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Cx45 regulation by kinases and impact of expression in heart failure.Journal of molecular and cellular cardiology · 2025Article
- Connexin hemichannels as candidate targets for cardioprotective and anti-arrhythmic treatments.The Journal of clinical investigation · 2023Review
- Rapid degradation of progressive ankylosis protein (ANKH) in craniometaphyseal dysplasia.Scientific reports · 2018Article
- BEST1 protein stability and degradation pathways differ between autosomal dominant Best disease and autosomal recessive bestrophinopathy accounting for the distinct retinal phenotypes.Human molecular genetics · 2018Article
- Altered translation initiation ofMolecular biology of the cell · 2018Article
- Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability.Circulation research · 2017Review
- Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A Novel Contributor to Inflammation?Mediators of inflammation · 2015Review
- Stat3 and gap junctions in normal and lung cancer cells.Cancers · 2014Article
- Regulation of cellular communication by signaling microdomains in the blood vessel wall.Pharmacological reviews · 2014Review
- Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system?Frontiers in pharmacology · 2013Review
- Gap junctions.Comprehensive Physiology · 2012Review
- Cx50 requires an intact PDZ-binding motif and ZO-1 for the formation of functional intercellular channels.Molecular biology of the cell · 2011Article
- Structure of the gap junction channel and its implications for its biological functions.Cellular and molecular life sciences : CMLS · 2011Review
- The potency of the fs260 connexin43 mutant to impair keratinocyte differentiation is distinct from other disease-linked connexin43 mutants.The Biochemical journal · 2010Article
- EKV mutant connexin 31 associated cell death is mediated by ER stress.Human molecular genetics · 2009Article
- Limiting transport steps and novel interactions of Connexin-43 along the secretory pathway.Histochemistry and cell biology · 2009Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
For all previously well-characterized oligomeric integral membrane proteins, folding, multisubunit assembly, and recognition of conformationally immature molecules for degradation occurs at their organelle of synthesis. This cannot, however, be the case for the gap junction-forming protein connexin43 (Cx43), which when endogenously expressed undergoes multisubunit assembly into connexons only after its transport to the trans-Golgi network. We have developed two novel assays to assess Cx43 folding and assembly: acquisition of resistance of disulfide bonds to reduction by extracellularly added DTT and Triton X-114 detergent phase partitioning. We show that Cx43 synthesized at physiologically relevant levels undergoes a multistep conformational maturation process in which folding of connexin monomers within the ER is a prerequisite for multisubunit assembly in the TGN. Similar results were obtained with Cx32, disproving the widely reported contention that the site of endogenous beta connexin assembly is the ER. Exogenous overexpression of Cx43, Cx32, or Cx26 allows these events to take place within the ER, the first example of the TGN and ER as alternative sites for oligomeric assembly. Our findings also constitute the first biochemical evidence that defective connexin folding is a cause of the human disorder X-linked Charcot-Marie-Tooth disease.
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Registered trials
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 OpenQuestion graph.