A functional interaction between the MAGUK protein hDlg and the gap junction protein Connexin 43 in cervical tumour cells

MacDonald, A.I. et al. (2012) A functional interaction between the MAGUK protein hDlg and the gap junction protein Connexin 43 in cervical tumour cells. Biochemical Journal, 446(1), pp. 9-21. (doi:10.1042/BJ20111144)

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Publisher's URL: http://dx.doi.org/10.1042/BJ20111144

Abstract

Gap junctions, composed of connexins, allow direct intercellular communication. Gap junctions are often lost during the development of malignancy, although the processes behind this are not fully understood. Connexin 43 (Cx43) is a widely expressed connexin with a long cytoplasmic C-terminal tail that contains several potential protein interaction domains. Previously, in a model of cervical carcinogenesis we showed loss of gap junctional communication correlated with relocalisation of Cx43 to the cytoplasm late in tumourigenesis. Now we demonstrate a similar pattern of altered expression for the Discs Large (hDlg) MAGUK family tumour suppressor protein in the cervical tumour cells, with partial co-localisation of Cx43 and hDlg in an endosomal/lysosomal compartment. Relocalisation of these proteins is not due to a general disruption of cell membrane integrity or connexin targeting. Cx43 (via its C-terminus) and hDlg interact directly in vitro and can form a complex in cells. This novel interaction requires the N and C-termini of hDlg. hDlg is not required for Cx43 internalisation in W12GPXY cells. Instead, hDlg appears to have a role in maintaining a cytoplasmic pool of Cx43. These results demonstrate that hDlg is a physiologically relevant regulator of Cx43 in transformed epithelial cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hodgins, Dr Malcolm and Graham, Professor Sheila and MacDonald, Dr Alasdair and Edward, Dr Michael
Authors: MacDonald, A.I., Sun, P., Hernandez-Lopez, H., Aasen, T., Hodgins, M., Edward, M., Roberts, S., Massimi, P., Thomas, M., Banks, L., and Graham, S.
Subjects:Q Science > QR Microbiology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Research Group:Graham SV
Journal Name:Biochemical Journal
Publisher:Portland Press Ltd.
ISSN:0264-6021
ISSN (Online):1470-8728
Published Online:01 June 2012

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438191The role of the hD1g, ZO-1 and hScrib tumour suppressors in control of Cx43 gap junctional intercellular communication in HPV-associated tumourigenesis.Sheila GrahamAssociation for International Cancer Research (AICR)08-0159MVLS III - CENTRE FOR VIRUS RESEARCH