The human Discs large protein (Dlg1) interacts with and maintains Connexin 43 at the plasma membrane in keratinocytes

Scott, H., Dong, L., Stevenson, A., MacDonald, A. I., Srinivasan, S., Massimi, P., Banks, L., Martin, P. E., Johnstone, S. R. and Graham, S. V. (2023) The human Discs large protein (Dlg1) interacts with and maintains Connexin 43 at the plasma membrane in keratinocytes. Journal of Cell Science, 136(11), jcs259984. (doi: 10.1242/jcs.259984) (PMID:37288673) (PMCID:PMC10309592)

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Abstract

Gap junction channels, composed of connexins, allow direct cell-to-cell communication. Connexin 43 (Cx43) is widely expressed in tissues, including the epidermis. In a previous study of human papillomavirus-positive cervical epithelial tumour cells, we identified Cx43 as a binding partner of the human homologue of Drosophila Discs large (Dlg1). Dlg1 is a member of the membrane associated-guanylate kinase (MAGUK) scaffolding protein family that is known to control cell shape and polarity. Here we show that Cx43 also interacts with Dlg1 in uninfected keratinocytes in vitro and in keratinocytes, dermal cells and adipocytes in normal human epidermis in vivo. Depletion of Dlg1 in keratinocytes did not alter Cx43 transcription but was associated with a reduction in Cx43 protein levels. Reduced Dlg1 levels in keratinocytes resulted in a reduction in Cx43 at the plasma membrane with a concomitant reduction in gap junctional intercellular communication and relocation of Cx43 to the Golgi compartment. Our data suggest a key role for Dlg1 in maintaining Cx43 at the plasma membrane in keratinocytes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stevenson, Mr Andrew and Graham, Professor Sheila and MacDonald, Dr Alasdair and Scott, Harry
Authors: Scott, H., Dong, L., Stevenson, A., MacDonald, A. I., Srinivasan, S., Massimi, P., Banks, L., Martin, P. E., Johnstone, S. R., and Graham, S. V.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Cell Science
Publisher:Company of Biologists
ISSN:0021-9533
ISSN (Online):1477-9137
Published Online:09 May 2023
Copyright Holders:Copyright © 2023 The Company of Biologists Ltd
First Published:First published in Journal of Cell Science 136(11):jcs259984
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
143102The role of the hD1g, ZO-1 and hScrib tumour suppressors in control of Cx43 gap junctional intercellular communication in HPV-associated tumourigenesis.Sheila GrahamWorldwide Cancer Research (WWCANRES)08-0159III - Bacteriology
308861Control of trafficking of the gap junction protein Connexin 43 in normal keratinocytes and healing wounds.Sheila GrahamBritish Skin Foundation (BSF)005_S_19III - Centre for Virus Research