ArticleeLife2023
Unconventional secretion of α-synuclein mediated by palmitoylated DNAJC5 oligomers.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Dopaminergic Identity of SH-SY5Y Cells Across Differentiation Protocols in Parkinson's Disease Research: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Glycoprotein-induced phase separation drives unconventional secretion of galectin-3.Nature communications · 2026Article
- Review
- SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids.NPJ Parkinson's disease · 2026Article
- Rsp5/NEDD4 and ESCRT regulate TDP-43 toxicity and turnover via an endolysosomal clearance mechanism.The Journal of cell biology · 2026Article
- Protocols for Monitoring Unconventional Protein Secretion Using Luminescence and Trapping Approaches.Current protocols · 2026Article
- The palmitoylation code in cell death signaling: from molecular mechanisms to therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- DNAJC5 promotes cisplatin resistance in epithelial ovarian cancer by autophagy induced by the BiP/IRE1α/XBP1 endoplasmic reticulum stress pathway.Scientific reports · 2025Article
- Beyond the Secretory Pathway: New Insights Into Protein Release.Traffic (Copenhagen, Denmark) · 2025Review
- N-type CaNPJ Parkinson's disease · 2025Article
- CHIP protects lysosomes from CLN4 mutant-induced membrane damage.Nature cell biology · 2025Article
- Palmitoylation: an emerging therapeutic target bridging physiology and disease.Cellular & molecular biology letters · 2025Review
- Elevated plasma levels of alpha-synuclein are dispensable for Parkinson's disease pathology.NPJ Parkinson's disease · 2025Article
- Neuronal lipofuscinosis caused by Kufs disease/CLN4 DNAJC5 mutations but not by a CSPα/DNAJC5 deficiency.Science advances · 2025Article
- DNAJC5 facilitates the proliferation and migration of lung adenocarcinoma cells by augmenting EGFR trafficking.Communications biology · 2025Article
- A Sensitive and Versatile Cell-Based Assay Combines Luminescence and Trapping Approaches to Monitor Unconventional Protein Secretion.Traffic (Copenhagen, Denmark) · 2025Article
- Review
- Enhanced secretion of the amyotrophic lateral sclerosis ALS-associated misfolded TDP-43 mediated by the ER-ubiquitin specific peptidase USP19.Cellular and molecular life sciences : CMLS · 2025Article
- Dnajc5b contributes to male fertility by maintaining the mitochondrial functions and autophagic homeostasis during spermiogenesis.Cellular and molecular life sciences : CMLS · 2025Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
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-induced oligomerization of DNAJC5. The secretion of endogenous α-syn mediated by DNAJC5 is also found in a human neuroblastoma cell line, SH-SY5Y, differentiated into neurons in the presence of retinoic acid, and in human-induced pluripotent stem cell-derived midbrain dopamine neurons. We propose that DNAJC5 forms a palmitoylated oligomer to accommodate and export α-syn.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.