PXD011553

PXD011553 is an original dataset announced via ProteomeXchange.

Title	A novel DHHC5/Golga7b palmitoyl-transferase complex regulates desmosome assembly and cell adhesion.
Description	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.
HostingRepository	PRIDE
AnnounceDate	2019-06-06
AnnouncementXML	Submission_2019-06-06_03:33:12.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Collins
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-01 02:59:04	ID requested
⏵ 1	2019-06-06 03:38:18	announced

Dataset with its publication pending

submitter keyword: DHHC5, palmitoylation, adhesion

Mark Collins
contact affiliation	Department of Biomedical Science & Centre for Membrane Interactions and Dynamics (CMIAD), Firth Court, Western Bank, University of Sheffield, S10 2TN, United Kingdom
contact email	mark.collins@sheffield.ac.uk
lab head
Mark Collins
contact affiliation	University of Sheffield
contact email	mark.collins@sheffield.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011553
     1. Label: PRIDE project
     2. Name: A novel DHHC5/Golga7b palmitoyl-transferase complex regulates desmosome assembly and cell adhesion.