Woodley, K.T. and Collins, M.O. orcid.org/0000-0002-7656-4975 (2019) S‐acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate cell adhesion. EMBO Reports, 20 (10). e47472. ISSN 1469-221X
Abstract
S‐acylation (palmitoylation) is the only fully reversible lipid modification of proteins; however, little is known about how protein S‐acyltransferases (PATs) that mediate it are regulated. DHHC5 is a PAT that is mainly localised at the plasma membrane with roles in synaptic plasticity, massive endocytosis and cancer cell growth/invasion. Here, we demonstrate that DHHC5 binds to and palmitoylates a novel accessory protein Golga7b. Palmitoylation of Golga7b prevents clathrin‐mediated endocytosis of DHHC5 and stabilises it at the plasma membrane. Proteomic analysis of the composition of DHHC5/Golga7b‐associated protein complexes reveals a striking enrichment in adhesion proteins, particularly components of desmosomes. We show that desmoglein‐2 and plakophilin‐3 are substrates of DHHC5 and that DHHC5 and Golga7b are required for localisation of desmoglein‐2 to the plasma membrane and for desmosomal patterning. Loss of DHHC5/Golga7b causes functional impairments in cell adhesion, suggesting these proteins have a wider role in cell adhesion beyond desmosome assembly. This work uncovers a novel mechanism of DHHC5 regulation by Golga7b and demonstrates a role for the DHHC5/Golga7b complex in the regulation of cell adhesion.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. This is an author-produced version of a paper subsequently published in EMBO Reports. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | cell adhesion; desmosome; DHHC5; Golga7b; palmitoylation |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Aug 2019 14:44 |
Last Modified: | 10 Dec 2021 09:05 |
Status: | Published |
Publisher: | EMBO Press |
Refereed: | Yes |
Identification Number: | 10.15252/embr.201847472 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:149783 |