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A novel DHHC5/Golga7b palmitoyl-transferase complex regulates desmosome assembly and cell adhesion.

ABSTRACT: Protein S-acylation, also known as palmitoylation, is the only fully reversible lipid post-translational modification of proteins however little is known about how the enzymes which mediate this modification are regulated and which cellular processes they control. DHHC5 is a plasma membrane localised palmitoyl acyltransferase (PAT) with important roles in the regulation of synaptic plasticity, massive palmitoylation-dependent endocytosis and cancer cell growth and invasion. Here we show that stabilisation of DHHC5 at the plasma membrane requires binding to and palmitoylation of an accessory protein Golga7b and that this interaction requires the palmitoylation of the C-terminal tail of DHHC5. We also found that blocking internalisation of DHHC5 from the plasma membrane is controlled by AP2-mediated clathrin endocytosis and that blocking this process traps DHHC5 at the plasma membrane. Affinity purification and mass spectrometry analysis of DHHC5-associated protein complexes uncovered a role for DHHC5 in demosomal formation and cell adhesion. We identified desmoglein-2 as a novel DHHC5 substrate and have demonstrated that DHHC5 is required for trafficking of desmoglein-2 to the plasma membrane and proper desmosomal patterning. This work has uncovered a novel mechanism of DHHC5 regulation by Golga7b and demonstrates a role for DHHC5 in the regulation of cell adhesion.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Mark Collins

LAB HEAD: Mark Collins

PROVIDER: PXD011553 | Pride | 2019-06-06

REPOSITORIES: Pride

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