{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wu S"],"funding":["NIH Biology and Biotechnology of Cell and Gene Therapy Training Program","Howard Hughes Medical Institute","Medical Research Council","Aligning Science Across Parkinson's","NIGMS NIH HHS","NIH HHS","Parkinson's UK"],"pagination":["e85837"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9876576"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["Alpha-synuclein (α-syn), a major component of Lewy bodies found in Parkinson's disease (PD) patients, has been found exported outside of cells and may mediate its toxicity via cell-to-cell transmission. Here, we reconstituted soluble, monomeric α-syn secretion by the expression of DnaJ homolog subfamily C member 5 (DNAJC5) in HEK293T cells. DNAJC5 undergoes palmitoylation and anchors on the membrane. Palmitoylation is essential for DNAJC5-induced α-syn secretion, and the secretion is not limited by substrate size or unfolding. Cytosolic α-syn is actively translocated and sequestered in an endosomal membrane compartment in a DNAJC5-dependent manner. Reduction of α-syn secretion caused by a palmitoylation-deficient mutation in DNAJC5 can be reversed by a membrane-targeting peptide fusion-ind"],"journal":["eLife"],"pubmed_title":["Unconventional secretion of α-synuclein mediated by palmitoylated DNAJC5 oligomers."],"pmcid":["PMC9876576"],"funding_grant_id":["MR/M024962/1","H-1301","K-1003","H-1102","MC_EX_MR/N50192X/1","MR/P007058/1","MR/N029453/1","NIH training program T32GM139780","G-1003","T32 GM139780","MR/L023784/2","G-0801","J-0901","ASAP-020370","J-1403"],"pubmed_authors":["Wade-Martins R","Schekman R","Wu S","Hernandez Villegas NC","Thomas-Wright I","Sirkis DW"],"additional_accession":[]},"is_claimable":false,"name":"Unconventional secretion of α-synuclein mediated by palmitoylated DNAJC5 oligomers.","description":"Alpha-synuclein (α-syn), a major component of Lewy bodies found in Parkinson's disease (PD) patients, has been found exported outside of cells and may mediate its toxicity via cell-to-cell transmission. Here, we reconstituted soluble, monomeric α-syn secretion by the expression of DnaJ homolog subfamily C member 5 (DNAJC5) in HEK293T cells. DNAJC5 undergoes palmitoylation and anchors on the membrane. Palmitoylation is essential for DNAJC5-induced α-syn secretion, and the secretion is not limited by substrate size or unfolding. Cytosolic α-syn is actively translocated and sequestered in an endosomal membrane compartment in a DNAJC5-dependent manner. Reduction of α-syn secretion caused by a palmitoylation-deficient mutation in DNAJC5 can be reversed by a membrane-targeting peptide fusion-ind","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-05-29T05:31:45.355Z","creation":"2025-02-18T23:45:10.471Z"},"accession":"S-EPMC9876576","cross_references":{"pubmed":["36626307"],"doi":["10.7554/eLife.85837"]}}