Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Connexin Hemichannels: Structure, Function, and Dysfunction
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Connexin Hemichannels: Structure, Function, and Dysfunction

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 July 2023) | Viewed by 6325

Special Issue Editor

Prof. Dr. Fabio Mammano

E-Mail Website1 Website2
Guest Editor
1. Department of Physics and Astronomy “G. Galilei”, University of Padova, 35131 Padova, Italy
2. CNR Institute of Biochemistry and Cell Biology, 00015 Monterotondo, Italy
Interests: connexins; Ca2+ signaling; photodynamic therapy for cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Connexin (Cx) hemichannels (HCs) are large pore hexameric structures that allow the exchange of ions, metabolites, and a variety of other molecules between cell cytoplasm and extracellular milieu. The opening of HCs promotes the diffusive release of paracrine messengers, including ATP, glutamate, prostaglandins, NAD(+), and glutathione. In several instances, molecules released through open HCs, most importantly ATP, may act as damage-associated molecular patterns (DAMPs), activating inflammatory pathways and promoting cell death. Point mutations that render HCs constitutively more active or abnormally active (referred to also as “leaky” HCs) have been implicated in numerous genetic diseases affecting the facial appearance, dentition (small and carious teeth), eyes (microphthalmia, microcornea), fingers (syndactyly), lens (cataracts), nervous system (myelination defects), heart (atrial fibrillation), inner ear (deafness), and skin (various disorders). In addition, the opening of wild-type (wt) HCs is associated with an impressive list of pathological conditions that affect a major proportion of the world population, including ischemia/stroke, Alzheimer’s disease, epilepsy, liver fibrosis and cirrhosis, nonalcoholic steatohepatitis, inflammation, and others. For these reasons, HC inhibitors are attracting growing interest as drug candidates.

Prof. Dr. Fabio Mammano
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cryoelectron microscopy
  • deafness
  • skin diseases
  • cataract
  • myelination defects
  • atrial fibrillation
  • muscular dystrophy
  • inflammation
  • acute lung injury
  • cancer
  • ischemia/stroke
  • Alzheimer’s disease
  • epilepsy
  • liver diseases

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

12 pages, 1861 KiB  
Article
Increased Hemichannel Activity Displayed by a Connexin43 Mutation Causing a Familial Connexinopathy Exhibiting Hypotrichosis with Follicular Keratosis and Hyperostosis
by Olivia E. Crouthamel, Leping Li, Michael T. Dilluvio and Thomas W. White
Int. J. Mol. Sci. 2023, 24(3), 2222; https://doi.org/10.3390/ijms24032222 - 22 Jan 2023
Cited by 1 | Viewed by 1723
Abstract
Mutations in the GJA1 gene that encodes connexin43 (Cx43) cause several rare genetic disorders, including diseases affecting the epidermis. Here, we examined the in vitro functional consequences of a Cx43 mutation, Cx43-G38E, linked to a novel human phenotype of hypotrichosis, follicular keratosis and [...] Read more.
Mutations in the GJA1 gene that encodes connexin43 (Cx43) cause several rare genetic disorders, including diseases affecting the epidermis. Here, we examined the in vitro functional consequences of a Cx43 mutation, Cx43-G38E, linked to a novel human phenotype of hypotrichosis, follicular keratosis and hyperostosis. We found that Cx43-G38E was efficiently translated in Xenopus oocytes and localized to gap junction plaques in transfected HeLa cells. Cx43-G38E formed functional gap junction channels with the same efficiency as wild-type Cx43 in Xenopus oocytes, although voltage gating of the gap junction channels was altered. Notably, Cx43-G38E significantly increased membrane current flow through the formation of active hemichannels when compared to wild-type Cx43. These data demonstrate the association of increased hemichannel activity to a connexin mutation linked to a skeletal-cutaneous phenotype, suggesting that augmented hemichannel activity could play a role in skin and skeletal disorders caused by human Cx43 mutations. Full article
(This article belongs to the Special Issue Connexin Hemichannels: Structure, Function, and Dysfunction)
►▼ Show Figures

Figure 1

Review

Jump to: Research

15 pages, 9307 KiB  
Review
Potential Role of Fenestrated Septa in Axonal Transport of Golgi Cisternae and Gap Junction Formation/Function
by Camillo Peracchia
Int. J. Mol. Sci. 2023, 24(6), 5385; https://doi.org/10.3390/ijms24065385 - 11 Mar 2023
Cited by 2 | Viewed by 1135
Abstract
Crayfish axons contain a system of parallel membranous cisternae spaced by ~2 μm and oriented perpendicularly to the axon’s long axis. Each cisterna is composed of two roughly parallel membranes, separated by a 150–400 Å wide space. The cisternae are interrupted by 500–600 [...] Read more.
Crayfish axons contain a system of parallel membranous cisternae spaced by ~2 μm and oriented perpendicularly to the axon’s long axis. Each cisterna is composed of two roughly parallel membranes, separated by a 150–400 Å wide space. The cisternae are interrupted by 500–600 Å pores, each occupied by a microtubule. Significantly, filaments, likely made of kinesin, often bridge the gap between the microtubule and the edge of the pore. Neighboring cisternae are linked by longitudinal membranous tubules. In small axons, the cisternae seem to be continuous across the axon, while in large axons they are intact only at the axon’s periphery. Due to the presence of pores, we have named these structures “Fenestrated Septa” (FS). Similar structures are also present in vertebrates, including mammals, proving that they are widely expressed in the animal kingdom. We propose that FS are components of the “anterograde transport” mechanism that moves cisternae of the Golgi apparatus (GA) toward the nerve ending by means of motor proteins, likely to be kinesins. In crayfish lateral giant axons, we believe that vesicles that bud off FS at the nerve ending contain gap junction hemichannels (innexons) for gap junction channel and hemichannel formation and function. Full article
(This article belongs to the Special Issue Connexin Hemichannels: Structure, Function, and Dysfunction)
►▼ Show Figures

Figure 1

24 pages, 6454 KiB  
Review
The Potential Role of Connexins in the Pathogenesis of Atherosclerosis
by Kajetan Kiełbowski, Estera Bakinowska and Andrzej Pawlik
Int. J. Mol. Sci. 2023, 24(3), 2600; https://doi.org/10.3390/ijms24032600 - 30 Jan 2023
Cited by 3 | Viewed by 3030
Abstract
Connexins (Cx) are members of a protein family which enable extracellular and intercellular communication through hemichannels and gap junctions (GJ), respectively. Cx take part in transporting important cell–cell messengers such as 3′,5′-cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP), and inositol 1,4,5-trisphosphate (IP3), among [...] Read more.
Connexins (Cx) are members of a protein family which enable extracellular and intercellular communication through hemichannels and gap junctions (GJ), respectively. Cx take part in transporting important cell–cell messengers such as 3′,5′-cyclic adenosine monophosphate (cAMP), adenosine triphosphate (ATP), and inositol 1,4,5-trisphosphate (IP3), among others. Therefore, they play a significant role in regulating cell homeostasis, proliferation, and differentiation. Alterations in Cx distribution, degradation, and post-translational modifications have been correlated with cancers, as well as cardiovascular and neurological diseases. Depending on the isoform, Cx have been shown either to promote or suppress the development of atherosclerosis, a progressive inflammatory disease affecting large and medium-sized arteries. Cx might contribute to the progression of the disease by enhancing endothelial dysfunction, monocyte recruitment, vascular smooth muscle cell (VSMC) activation, or by inhibiting VSMC autophagy. Inhibition or modulation of the expression of specific isoforms could suppress atherosclerotic plaque formation and diminish pro-inflammatory conditions. A better understanding of the complexity of atherosclerosis pathophysiology linked with Cx could result in developing novel therapeutic strategies. This review aims to present the role of Cx in the pathogenesis of atherosclerosis and discusses whether they can become novel therapeutic targets. Full article
(This article belongs to the Special Issue Connexin Hemichannels: Structure, Function, and Dysfunction)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop