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S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate desmosome assembly and cell adhesion

Keith T. Woodley, View ORCID ProfileMark O. Collins
doi: https://doi.org/10.1101/481861
Keith T. Woodley
1Department of Biomedical Science & Centre for Membrane Interactions and Dynamics (CMIAD), Firth Court, Western Bank, University of Sheffield, S10 2TN, United Kingdom.
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Mark O. Collins
1Department of Biomedical Science & Centre for Membrane Interactions and Dynamics (CMIAD), Firth Court, Western Bank, University of Sheffield, S10 2TN, United Kingdom.
2Faculty of Science Mass Spectrometry Centre, University of Sheffield, Brook Hill Road, Sheffield, S3 7HF, United Kingdom.
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  • ORCID record for Mark O. Collins
  • For correspondence: mark.collins@sheffield.ac.uk
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Abstract

S-acylation 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 plasma membrane-localised PAT with roles in synaptic plasticity, massive endocytosis and cancer cell growth/invasion. Here we demonstrate that stabilisation of DHHC5 at the plasma membrane requires binding to and palmitoylation of an accessory protein Golga7b. This interaction requires the palmitoylation of the C-terminus of DHHC5 which regulates the internalisation of DHHC5 from the plasma membrane. Proteomic analysis of DHHC5/Golga7b-associated protein complexes reveals an enrichment in adhesion proteins, particularly components of desmosomes. We show that Desmoglein-2 and Plakophilin-3 are substrates of DHHC5 and that DHHC5/Golga7b are required for localisation of Desmoglein-2 to the plasma membrane and 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.

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Posted December 06, 2018.
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S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate desmosome assembly and cell adhesion
Keith T. Woodley, Mark O. Collins
bioRxiv 481861; doi: https://doi.org/10.1101/481861
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S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate desmosome assembly and cell adhesion
Keith T. Woodley, Mark O. Collins
bioRxiv 481861; doi: https://doi.org/10.1101/481861

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