Claudin-2: Roles beyond Permeability Functions.


Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
12 Nov 2019
Historique:
received: 13 10 2019
revised: 08 11 2019
accepted: 09 11 2019
entrez: 16 11 2019
pubmed: 16 11 2019
medline: 2 4 2020
Statut: epublish

Résumé

Claudin-2 is expressed in the tight junctions of leaky epithelia, where it forms cation-selective and water permeable paracellular channels. Its abundance is under fine control by a complex signaling network that affects both its synthesis and turnover in response to various environmental inputs. Claudin-2 expression is dysregulated in many pathologies including cancer, inflammation, and fibrosis. Claudin-2 has a key role in energy-efficient ion and water transport in the proximal tubules of the kidneys and in the gut. Importantly, strong evidence now also supports a role for this protein as a modulator of vital cellular events relevant to diseases. Signaling pathways that are overactivated in diseases can alter claudin-2 expression, and a good correlation exists between disease stage and claudin-2 abundance. Further, loss- and gain-of-function studies showed that primary changes in claudin-2 expression impact vital cellular processes such as proliferation, migration, and cell fate determination. These effects appear to be mediated by alterations in key signaling pathways. The specific mechanisms linking claudin-2 to these changes remain poorly understood, but adapters binding to the intracellular portion of claudin-2 may play a key role. Thus, dysregulation of claudin-2 may contribute to the generation, maintenance, and/or progression of diseases through both permeability-dependent and -independent mechanisms. The aim of this review is to provide an overview of the properties, regulation, and functions of claudin-2, with a special emphasis on its signal-modulating effects and possible role in diseases.

Identifiants

pubmed: 31726679
pii: ijms20225655
doi: 10.3390/ijms20225655
pmc: PMC6888627
pii:
doi:

Substances chimiques

CLDN2 protein, human 0
Claudins 0
Neoplasm Proteins 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : CIHR
ID : PJT-149058
Pays : Canada
Organisme : CIHR
ID : MOP-142409
Pays : Canada
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : RGPIN-2017-06517
Organisme : Kidney Foundation of Canada
ID : n/a

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Auteurs

Shruthi Venugopal (S)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital and Department of Surgery, University of Toronto, Toronto, ON M5B 1W8, Canada.

Shaista Anwer (S)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital and Department of Surgery, University of Toronto, Toronto, ON M5B 1W8, Canada.

Katalin Szászi (K)

Keenan Research Centre for Biomedical Science of the St. Michael's Hospital and Department of Surgery, University of Toronto, Toronto, ON M5B 1W8, Canada.

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