Gap junction gene and protein families: Connexins, innexins, and pannexins

Beyer, Eric C.; Berthoud, Viviana M.

doi:10.1016/j.bbamem.2017.05.016

Cited by 164 publications

(139 citation statements)

References 57 publications

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“…It has been reported that these pathological conditions are related to the disruption of gap junction-mediated intercellular communications [25]. Gap junctions are composed of intercellular channels formed by connexins [26]. Increasing evidence indicates the importance of connexins in modulating the severity of inflammatory disease [27].…”

Section: Discussionmentioning

confidence: 99%

Fangjifuling Ameliorates Lipopolysaccharide-Induced Renal Injury via Inhibition of Inflammatory and Apoptotic Response in Mice

Su¹,

Yu²,

Sheng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Acute kidney injury (AKI) is a frequent and serious complication of sepsis; however, there is no effective treatment for it. FangJiFuling (FF) decoction is widely used to treat acute glomerulonephritis and nephritic syndrome in the clinical setting. Methods: On the basis of its anti-inflammatory properties, the renoprotective effect of FF on a mouse model of lipopolysaccharide (LPS)-induced AKI was investigated. Major compounds were identified in FF with high-performance liquid chromatography. A bioinformatics analysis tool was used to predict target genes. Quantitative real-time PCR and western blot analyses were performed to validate the targets. Furthermore, the expression of a target gene was silenced by small interfering RNA-mediated knockdown in vitro. Results: Bioinformatics analysis indicated that inflammation, apoptosis, and cell junction were closely related to the renoprotective effects of FF. Validation was confirmed by an in vivo test. A reduction of inflammatory cell infiltration and inflammatory cytokine mRNA expression (iNOS, NF-κB, MCP-1, and TNF-α) following the administration of FF (50 mg/kg) was observed in LPS-treated renal tissue. In addition, FF treatment suppressed mitochondrial-mediated apoptosis by regulating the Bax/Bcl-2 ratio in LPS-induced renal injury. Silencing Cx43, a cell-to-cell junction protein, was found to enhance the protective effect of FF against LPS-induced renal injury. Conclusion: Our study suggests that FF exhibits a renoprotective effect against LPS-induced inflammatory and apoptotic responses. In addition, Cx43 might be involved in these processes. These findings indicate the potential role of FF as a natural renoprotective product.

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Section: Discussionmentioning

confidence: 99%

Fangjifuling Ameliorates Lipopolysaccharide-Induced Renal Injury via Inhibition of Inflammatory and Apoptotic Response in Mice

Su¹,

Yu²,

Sheng³

et al. 2018

Cell Physiol Biochem

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“…Gap junctions are plasma membrane domains containing arrays of intercellular channels that allow for the direct transfer of ions and small molecules (< ~ 1.2 kDa) between cells [1]. In vertebrates, gap junction channels are formed by a family of transmembrane proteins called connexins, which in humans constitutes 20 members [2]. Connexins are expressed in almost all cell types of the human body and have essential roles during development as well as in the adult organism.…”

Section: Introductionmentioning

confidence: 99%

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

Totland

Rasmussen

Knudsen

et al. 2019

Cell. Mol. Life Sci.

110

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Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junctions have a wide diversity of physiological functions, playing critical roles in both excitable and non-excitable tissues. Gap junction channels are formed by integral membrane proteins called connexins. Inherited or acquired alterations in connexins are associated with numerous diseases, including heart failure, neuropathologies, deafness, skin disorders, cataracts and cancer. Gap junctions are highly dynamic structures and by modulating the turnover rate of connexins, cells can rapidly alter the number of gap junction channels at the plasma membrane in response to extracellular or intracellular cues. Increasing evidence suggests that ubiquitination has important roles in the regulation of endoplasmic reticulum-associated degradation of connexins as well as in the modulation of gap junction endocytosis and post-endocytic sorting of connexins to lysosomes. In recent years, researchers have also started to provide insights into the physiological roles of connexin ubiquitination in specific tissue types. This review provides an overview of the advances made in understanding the roles of connexin ubiquitination in the regulation of gap junction intercellular communication and discusses the emerging physiological and pathophysiological implications of these processes.

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“…The connexin genes form a close family displaying a large degree of amino acid identity and similarity within both the extracellular and transmembrane regions [10]. To date, the family of connexin genes is composed of 20 members within the mouse genome and 21 within the human genome, with 19 having clearly identifiable orthologs between both [11]. The genes are named starting with an abbreviation for gap junction, followed by their corresponding subgroup and order of discovery.…”

Section: Introductionmentioning

confidence: 99%

Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease

Cocozzelli

White

2019

IJMS

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Gap junctional channels are specialized components of the cellular membrane that allow the intercellular passage of small metabolites, ions, and second messengers to maintain homeostasis. They are comprised of members of the connexin gene family that encode a wide array of proteins that are expressed in nearly every tissue type. Cx43 is perceived to be the most broadly expressed connexin in humans, with several genetic skin diseases being linked to Cx43 mutations specifically. These mutations, in large, produce a gain of functional hemichannels that contribute to the phenotypes of Erythrokeratoderma Variabilis et Progressiva (EKVP), Palmoplantar Keratodemra Congenital Alopecia-1 (PPKCA1), and others that produce large conductance and increased permselectivity in otherwise quiescent structures. Gaining functional hemichannels can have adverse effects in the skin, inducing apoptosis via Ca2+ overload or increased ATP permeability. Here, we review the link between Cx43 and skin disease. We aim to provide insight into the mechanisms regulating the normal and pathophysiological gating of these essential proteins, as well as address current therapeutic strategies. We also demonstrate that transient transfection of neuro-2a (N2a) cells with mutant Cx43 cDNA resulted in increased hemichannel activity compared to wild-type Cx43 and untransfected cells, which is consistent with other studies in the current literature.

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Gap junction gene and protein families: Connexins, innexins, and pannexins

Cited by 164 publications

References 57 publications

Fangjifuling Ameliorates Lipopolysaccharide-Induced Renal Injury via Inhibition of Inflammatory and Apoptotic Response in Mice

Fangjifuling Ameliorates Lipopolysaccharide-Induced Renal Injury via Inhibition of Inflammatory and Apoptotic Response in Mice

Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications

Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease

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