ArticleThe Journal of biological chemistry2012
Palmitoylation-induced aggregation of cysteine-string protein mutants that cause neuronal ceroid lipofuscinosis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Uncovering the role of the Hsp40 family member cysteine string protein-α in mouse platelets.Blood advances · 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
- Review
- Cysteine string protein α and a link between rare and common neurodegenerative dementias.NPJ dementia · 2025Review
- Inhibition of zDHHC7-driven protein S-palmitoylation prevents cognitive deficits in an experimental model of Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Proximity labelling reveals effects of disease-causing mutation on the DNAJC5/cysteine string protein α interactome.The Biochemical journal · 2024Article
- L116 Deletion in CSPα Promotes α-Synuclein Aggregation and Neurodegeneration.Molecular neurobiology · 2024Article
- Therapeutic development targeting host heparan sulfate proteoglycan in SARS-CoV-2 infection.Frontiers in medicine · 2024Review
- A Caenorhabditis elegans model of autosomal dominant adult-onset neuronal ceroid lipofuscinosis identifies ethosuximide as a potential therapeutic.Human molecular genetics · 2023Article
- Extracellular chaperone networks and the export of J-domain proteins.The Journal of biological chemistry · 2023Review
- Article
- Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation.Autophagy · 2023Article
- CSPα in neurodegenerative diseases.Frontiers in aging neuroscience · 2022Review
- Adult-Onset Neuronal Ceroid Lipofuscinosis With a NovelFrontiers in aging neuroscience · 2022Article
- The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis.Nature communications · 2021Article
- Autosomal dominant neuronal ceroid lipofuscinosis: Clinical features and molecular basis.Clinical genetics · 2021Review
- Endosomal Trafficking in Alzheimer's Disease, Parkinson's Disease, and Neuronal Ceroid Lipofuscinosis.Molecular and cellular biology · 2020Review
- Structure and Mechanism of DHHC Protein Acyltransferases.Journal of molecular biology · 2020Review
- Aggregation of mutant cysteine string protein-α via Fe-S cluster binding is mitigated by iron chelators.Nature structural & molecular biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Recently, mutations in the DNAJC5 gene encoding cysteine-string protein α (CSPα) were identified to cause the neurodegenerative disorder adult-onset neuronal ceroid lipofuscinosis. The disease-causing mutations (L115R or ΔL116) occur within the cysteine-string domain, a region of the protein that is post-translationally modified by extensive palmitoylation. Here we demonstrate that L115R and ΔL116 mutant proteins are mistargeted in neuroendocrine cells and form SDS-resistant aggregates, concordant with the properties of other mutant proteins linked to neurodegenerative disorders. The mutant aggregates are membrane-associated and incorporate palmitate. Indeed, co-expression of palmitoyltransferase enzymes promoted the aggregation of the CSPα mutants, and chemical depalmitoylation solubilized the aggregates, demonstrating that aggregation is induced and maintained by palmitoylation. In agreement with these observations, SDS-resistant CSPα aggregates were present in brain samples from patients carrying the L115R mutation and were depleted by chemical depalmitoylation. In summary, this study identifies a novel interplay between genetic mutations and palmitoylation in driving aggregation of CSPα mutant proteins. We propose that this palmitoylation-induced aggregation of mutant CSPα proteins may underlie the development of adult-onset neuronal ceroid lipofuscinosis in affected families.
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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.