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Roles of connexins and pannexins in digestive homeostasis

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Abstract

Connexin proteins are abundantly present in the digestive system. They primarily form gap junctions, which control the intercellular exchange of critical homeostasis regulators. By doing so, gap junctions drive a plethora of gastrointestinal and hepatic functional features, including gastric and gut motility, gastric acid secretion, intestinal innate immune defense, xenobiotic biotransformation, glycogenolysis, bile secretion, ammonia detoxification and plasma protein synthesis. In the last decade, it has become clear that connexin hemichannels, which are the structural precursors of gap junctions, also provide a pathway for cellular communication, namely between the cytosol and the extracellular environment. Although merely pathological functions have been described, some physiological roles have been attributed to connexin hemichannels, in particular in the modulation of colonic motility. This equally holds true for cellular channels composed of pannexins, connexin-like proteins recently identified in the intestine and the liver, which have become acknowledged key players in inflammatory processes and that have been proposed to control colonic motility, secretion and blood flow.

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Abbreviations

ATP:

Adenosine triphosphate

cAMP:

Cyclic adenosine monophosphate

CL:

Cytoplasmic loop

CT:

Cytoplasmic carboxy tail

Cx:

Connexin

EL:

Extracellular loop

GJIC:

Gap junctional intercellular communication

IP3 :

Inositol triphosphate

NT:

Cytoplasmic amino tail

Panx:

Pannexin

TM:

Transmembrane domain

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Acknowledgments

This work was financially supported by the grants of Agency for Innovation by Science and Technology in Flanders (IWT), the University Hospital of the Vrije Universiteit Brussel-Belgium (“Willy Gepts Fonds” UZ-VUB), the Fund for Scientific Research-Flanders (FWO Grants G009514 N and G010214 N), the European Research Council (ERC Starting Grant 335476), the University of São Paulo-Brazil and the Foundation for Research Support of the State of São Paulo (FAPESP SPEC Grant 2013/50420-6).

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The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

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  1. Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium

    Michaël Maes, Sara Crespo Yanguas, Joost Willebrords & Mathieu Vinken

  2. Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

    Bruno Cogliati

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Maes, M., Cogliati, B., Crespo Yanguas, S. et al. Roles of connexins and pannexins in digestive homeostasis. Cell. Mol. Life Sci. 72, 2809–2821 (2015). https://doi.org/10.1007/s00018-015-1961-8

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