Gap Junctions in Development and Disease

Winterhager, Elke

doi:10.1007/3-540-28621-7

Cited by 6 publications

(2 citation statements)

References 454 publications

(809 reference statements)

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“…and EL2 C(1)zzzvC( 2)vzzvvC(3) sequences, in which 100 % of C(1), C(2), C(3), >80 % of X residues (v) and <80 % of X residues (z) are conserved 58 . In view of conserved extracellular cysteines and extensively homologous protein sequences of Cx isoforms, along with their mutations, phosphorylated and ubiquitinated derivatives 43,44,47,92,93 , it seems likely that several homo-and heteromeric CxGJ . CC-BY-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

Section: Spatio-temporal Configuration Dynamics Of Paired Cx43hc-hc M...mentioning

confidence: 99%

“…GJ channels have received attention due to their pivotal roles in various physiological and pathophysiological processes [38][39][40][41][42][43][44][45][46][47][48][49][50][51] , such as epilepsy 52 , Alzheimer disease 53 or cancer [54][55][56] . However, the lack of Cx subtype-specific inhibitors for these channels has hindered their exploitation in pharmacological strategies.…”

Section: Introductionmentioning

confidence: 99%

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Simulation of gap junction formation reveals critical role of cysteines in connexon coupling

Héja

Simon

Kardos

2023

Preprint

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Despite the fundamental functions of connexin gap junctions (CxGJs), understanding of molecular mechanisms, governing intercellular CxGJ formation by coupling of connexon hemichannels (CxHCs, connexons) is still in infancy. In silico simulation of intercellular connexon coupling of two Cx43HC models, embedded in membrane bilayers (Cx43HC-HC) successfully modelled the emergence of trans-gap junctional (trans-GJ) stabilization centers (SCs). Investigating the molecular determinants shaping the HC-HC interface, we revealed that the exceptionally high number of cysteine residues located at the interface play a pivotal role in the stabilization of HC and GJ structures. Opening of the disulphide bonds between these cysteines resulted in disappearance of trans-GJ SCs in the Cx43GJ model. In contrast, the Cx43HC form was found to be consistent with open disulphide bonds. Finally, we have shown that the presence of an adjoining HC contributes to disulphide formation and consequently to the emergence of trans-GJ H-bonds. Our results suggest that several connexon channels in vertebrates may undertake intercellular connexon coupling similarly and may bring forward to the targeting of CxGJ-specific coupling.

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