Connexins, Pannexins, and Homologous Channel-Forming Proteins

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Proteins".

Deadline for manuscript submissions: 30 August 2024 | Viewed by 3126

Special Issue Editors

Special Issue Information

Dear Colleagues,

Intercellular communication plays essential roles in several physiological and pathological processes. One of the most important mechanisms for intercellular communication in mammalian cells is the one mediated by Connexin or Pannexins. Those proteins constitute families of transmembrane proteins, which form gap junction channels and/or hemichannels, which communicate the cytoplasm of contacting cells or allow the sharing of small molecules such as ATP and glutamate between the cytoplasm of contacting cells or between the intra the extracellular milieu, respectively. Under physiological conditions gap junctions coordinate metabolic and electrical cell responses, whereas hemichannels present low activity under resting conditions and present transient increases upon specific changes in the microenvironment. In contrast, under pathological conditions, the activity of gap junction is drastically diminished and that of hemichannels is augmented. Functional homologous channels have been found in insects (innexins) and unicellular organisms such as Trypanosoma cruzi (Unnexins). The study of these proteins (structurally and functionally) has been fundamental for the understanding of the basis of several human diseases (e.g., deafness neurodegenerative disease, neurodevelopmental diseases, and neuromuscular diseases), and this knowledge has promoted the discovery of new tools to improve cell and tissue functions.

Since 1993, Chilean scientists have contributed enormously to the understanding of how these proteins work, thanks to the use of diverse techniques such as molecular biology, cellular biology, electrophysiology, cell models, and molecular dynamics, among many others. Close to 80 Chilean scientists attended the first summit of Connexins/Pannexns/Innexins and Unnexins performed at Universidad del Desarrollo (UDD), Santiago, Chile on January 16, 2023. They cover a wide range of interesting issues related to the regulation, function, and relevance of cell-cell communication proteins including drug design to selectively affect the functional state of the channels. This event was proposed to be celebrated every two years at different Chilean academic institutions and will be open to everyone interested in participating.

This Special Issue welcomes submissions of manuscripts, original research, comprehensive reviews, communications on this topic, and the extended and expanded versions of the Proceedings papers from the summit.

Dr. Mauricio A. Retamal
Prof. Dr. Juan Carlos Saéz
Guest Editors

Manuscript Submission Information

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Keywords

  • gap junctions
  • hemichannels
  • connexins
  • pannexins
  • innexins
  • unnexins
  • paracrine
  • autocrine

Published Papers (2 papers)

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Research

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17 pages, 1646 KiB  
Article
Pannexin-1 Modulates Inhibitory Transmission and Hippocampal Synaptic Plasticity
by Francisca García-Rojas, Carolina Flores-Muñoz, Odra Santander, Pamela Solis, Agustín D. Martínez, Álvaro O. Ardiles and Marco Fuenzalida
Biomolecules 2023, 13(6), 887; https://doi.org/10.3390/biom13060887 - 25 May 2023
Cited by 2 | Viewed by 1599
Abstract
Pannexin-1 (Panx1) hemichannel is a non-selective transmembrane channel that may play important roles in intercellular signaling by allowing the permeation of ions and metabolites, such as ATP. Although recent evidence shows that the Panx1 hemichannel is involved in controlling excitatory synaptic transmission, the [...] Read more.
Pannexin-1 (Panx1) hemichannel is a non-selective transmembrane channel that may play important roles in intercellular signaling by allowing the permeation of ions and metabolites, such as ATP. Although recent evidence shows that the Panx1 hemichannel is involved in controlling excitatory synaptic transmission, the role of Panx1 in inhibitory transmission remains unknown. Here, we studied the contribution of Panx1 to the GABAergic synaptic efficacy onto CA1 pyramidal neurons (PyNs) by using patch–clamp recordings and pharmacological approaches in wild-type and Panx1 knock-out (Panx1-KO) mice. We reported that blockage of the Panx1 hemichannel with the mimetic peptide 10Panx1 increases the synaptic level of endocannabinoids (eCB) and the activation of cannabinoid receptors type 1 (CB1Rs), which results in a decrease in hippocampal GABAergic efficacy, shifting excitation/inhibition (E/I) balance toward excitation and facilitating the induction of long-term potentiation. Our finding provides important insight unveiling that Panx1 can strongly influence the overall neuronal excitability and play a key role in shaping synaptic changes affecting the amplitude and direction of plasticity, as well as learning and memory processes. Full article
(This article belongs to the Special Issue Connexins, Pannexins, and Homologous Channel-Forming Proteins)
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Review

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16 pages, 1748 KiB  
Review
Connexins in Cancer, the Possible Role of Connexin46 as a Cancer Stem Cell-Determining Protein
by Isidora M. León-Fuentes, María G. Salgado-Gil, María S. Novoa and Mauricio A. Retamal
Biomolecules 2023, 13(10), 1460; https://doi.org/10.3390/biom13101460 - 27 Sep 2023
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Abstract
Cancer is a widespread and incurable disease caused by genetic mutations, leading to uncontrolled cell proliferation and metastasis. Connexins (Cx) are transmembrane proteins that facilitate intercellular communication via hemichannels and gap junction channels. Among them, Cx46 is found mostly in the eye lens. [...] Read more.
Cancer is a widespread and incurable disease caused by genetic mutations, leading to uncontrolled cell proliferation and metastasis. Connexins (Cx) are transmembrane proteins that facilitate intercellular communication via hemichannels and gap junction channels. Among them, Cx46 is found mostly in the eye lens. However, in pathological conditions, Cx46 has been observed in various types of cancers, such as glioblastoma, melanoma, and breast cancer. It has been demonstrated that elevated Cx46 levels in breast cancer contribute to cellular resistance to hypoxia, and it is an enhancer of cancer aggressiveness supporting a pro-tumoral role. Accordingly, Cx46 is associated with an increase in cancer stem cell phenotype. These cells display radio- and chemoresistance, high proliferative abilities, self-renewal, and differentiation capacities. This review aims to consolidate the knowledge of the relationship between Cx46, its role in forming hemichannels and gap junctions, and its connection with cancer and cancer stem cells. Full article
(This article belongs to the Special Issue Connexins, Pannexins, and Homologous Channel-Forming Proteins)
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