{"database":"biostudies-other","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Mr. Keith, T Woodley"],"funding":["UK Research and Innovation | Biotechnology and Biological Sciences Research Council (BBSRC)"],"journal":["EMBO Reports"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMBOR-2018-47472V1"],"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 stabilizes 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/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."],"repository":["biostudies-other"],"funding_grant_id":["BB/P021689/1"],"pubmed_authors":["Dr. Mark, Oliver Collins","Mr. Keith, T Woodley"],"additional_accession":[]},"is_claimable":false,"name":"S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate cell adhesion","description":"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 stabilizes 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/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.","dates":{"modification":"2020-01-16T21:00:12Z","creation":"2020-01-16T21:00:12Z"},"accession":"S-SCDT-EMBOR-2018-47472V1","cross_references":{"doi":["10.15252/embr.201847472"]}}