Non-canonical roles of connexins

Campenhout, Raf Van; Cooreman, Axelle; Leroy, Kaat; Rusiecka, Olga M.; Brantegem, Pieter Van; Annaert, Pieter; Devoogdt, Nick; Cogliati, Bruno; Kwak, Brenda R.; Vinken, Mathieu

doi:10.1016/j.pbiomolbio.2020.03.002

Cited by 16 publications

(16 citation statements)

References 87 publications

(106 reference statements)

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“…Cx43 is subject to post-translational modifications (PTMs), which not only affect the trafficking of connexons to the cell membrane and their insertion into gap junction plaques, but also the gating properties and permeability of gap junction channels and hemi-channels [40]. Moreover, emerging data suggest channel-independent roles for the Cx family of proteins, such as the regulation of gene transcription through transcription factor hijacking or acting as a scaffolding protein for regulating the dynamics of other proteins at the cell membrane [46,47].…”

Section: Canonical Role Of Connexin43 In I/r Injury and Cardioprotectionmentioning

confidence: 99%

Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection

et al. 2020

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Since the mid-20th century, ischemic heart disease has been the world’s leading cause of death. Developing effective clinical cardioprotection strategies would make a significant impact in improving both quality of life and longevity in the worldwide population. Both ex vivo and in vivo animal models of cardiac ischemia/reperfusion (I/R) injury are robustly used in research. Connexin43 (Cx43), the predominant gap junction channel-forming protein in cardiomyocytes, has emerged as a cardioprotective target. Cx43 posttranslational modifications as well as cellular distribution are altered during cardiac reperfusion injury, inducing phosphorylation states and localization detrimental to maintaining intercellular communication and cardiac conduction. Pre- (before ischemia) and post- (after ischemia but before reperfusion) conditioning can abrogate this injury process, preserving Cx43 and reducing cell death. Pre-/post-conditioning has been shown to largely rely on the presence of Cx43, including mitochondrial Cx43, which is implicated to play a major role in pre-conditioning. Posttranslational modifications of Cx43 after injury alter the protein interactome, inducing negative protein cascades and altering protein trafficking, which then causes further damage post-I/R injury. Recently, several peptides based on the Cx43 sequence have been found to successfully diminish cardiac injury in pre-clinical studies.

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Section: Canonical Role Of Connexin43 In I/r Injury and Cardioprotectionmentioning

confidence: 99%

Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection

et al. 2020

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“…In the last years, it has been noted that not only Cx expression levels but also the Cx channel-dependent and channel-independent functions must be considered in order to decipher their role in cancer. Thus, Cxs exert their channel-independent way of action mainly through the interaction with other proteins, and the vast majority of these protein interactions are mediated by the Cx C-terminal (hereafter named as free CT) (Giepmans et al, 2001;Hervé et al, 2004;Jiang & Gu, 2005;Kanemitsu et al, 1997;Moorby & Patel, 2001;Sorgen et al, 2018;Van Campenhout et al, 2020;Zhou & Jiang, 2014). Thus for example, in triple-negative breast cancer cells, Cx26 interaction with Nanog promotes CSC renewal (Thiagarajan et al, 2018).…”

Section: How Cx46 Could Modulate Melanoma Cell Aggressiveness?mentioning

confidence: 99%

Connexins in melanoma: Potential role of Cx46 in its aggressiveness

Orellana

Tittarelli

Retamal

2020

Pigment Cell Melanoma Res

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The skin is the largest organ in the human body, and it is constantly exposed to environmental insults, such as bacteria, viruses, air/water pollution, sunrays (Rodrigues et al., 2019). Three layers compose the skin: the epidermis, the dermis, and the hypodermis (Debeer et al., 2013). The epidermis is the outer layer of the skin, and it is the first barrier that protects the organism from external elements. Keratinocytes, melanocytes, Langerhans cells, and Merkel cells, arranged in five cellular layers, compose the epidermis. The deepest layer of the epidermis, the stratum basale, is constantly producing new cells that differentiate and migrate to the most external layer, named as stratum corneum, where they lose their nucleus and merge. In the normal skin, the most external cells detach constantly, taking around 2 weeks from birth in the Stratum basale to their loss in the Stratum corneum. The dermis is below the Stratum basale and has several functions, such as to feed the epidermis, to

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“…Over the past two decades, it has become clear that connexin hemichannels also provide an autonomous communication pathway for communication on their own, independent of their role as structural precursors of gap junctions [4]. While gap junctions mediate intercellular communication, connexin hemichannels support the transport of messengers between the cytosol and the extracellular environment.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms Underlying Connexin Hemichannel Activation in Disease

Campenhout

Gomes

Groof

et al. 2021

IJMS

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Gap junctions and connexin hemichannels mediate intercellular and extracellular communication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease. Open connexin hemichannels indeed mediate the transport of messengers between the cytosol and extracellular environment and, by doing so, fuel inflammation and cell death in a plethora of diseases. The present mini-review discusses the mechanisms involved in the activation of connexin hemichannels during pathology.

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Non-canonical roles of connexins

Cited by 16 publications

References 87 publications

Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection

Canonical and Non-Canonical Roles of Connexin43 in Cardioprotection

Connexins in melanoma: Potential role of Cx46 in its aggressiveness

Mechanisms Underlying Connexin Hemichannel Activation in Disease

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