ArticleThe Journal of biological chemistry2008
Palmitoylation and membrane interactions of the neuroprotective chaperone cysteine-string protein.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 126 citations in OpenAlex.
- Article
- Cysteine string protein α and a link between rare and common neurodegenerative dementias.NPJ dementia · 2025Review
- S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi.eLife · 2024Article
- Palmitoylation of synaptic proteins: roles in functional regulation and pathogenesis of neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- Tissue distribution of cysteine string protein/DNAJC5 in C. elegans analysed by CRISPR/Cas9-mediated tagging of endogenous DNJ-14.Cell and tissue research · 2024Article
- Proximity labelling reveals effects of disease-causing mutation on the DNAJC5/cysteine string protein α interactome.The Biochemical journal · 2024Article
- A Caenorhabditis elegans model of autosomal dominant adult-onset neuronal ceroid lipofuscinosis identifies ethosuximide as a potential therapeutic.Human molecular genetics · 2023Article
- Efficient cell death mediated by bioengineered killer extracellular vesicles.Scientific reports · 2023Article
- Article
- Lipidation states orchestrate CLICK-III/CaMKIγ's stepwise association with Golgi and rafts-enriched membranes and specify its functional coupling to STEF-Rac1-dependent neurite extension.Frontiers in cellular neuroscience · 2023Article
- Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation.Autophagy · 2023Article
- Adult-Onset Neuronal Ceroid Lipofuscinosis With a NovelFrontiers in aging neuroscience · 2022Article
- CSPα in neurodegenerative diseases.Frontiers in aging neuroscience · 2022Review
- Safeguarding Lysosomal Homeostasis by DNAJC5/CSPα-Mediated Unconventional Protein Secretion and Endosomal Microautophagy.Frontiers in cell and developmental biology · 2022Review
- The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis.Nature communications · 2021Article
- Regulatory effects of protein S-acylation on insulin secretion and insulin action.Open biology · 2021Review
- The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis.International journal of molecular sciences · 2021Review
- Protein S-Palmitoylation and Lung Diseases.Advances in experimental medicine and biology · 2021Article
- Identification of key features required for efficient S-acylation and plasma membrane targeting of sprouty-2.Journal of cell science · 2020Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Cysteine-string protein (CSP) is an extensively palmitoylated DnaJ-family chaperone, which exerts an important neuroprotective function. Palmitoylation is required for the intracellular sorting and function of CSP, and thus it is important to understand how this essential modification of CSP is regulated. Recent work identified 23 putative palmitoyl transferases containing a conserved DHHC domain in mammalian cells, and here we show that palmitoylation of CSP is enhanced specifically by co-expression of the Golgi-localized palmitoyl transferases DHHC3, DHHC7, DHHC15, or DHHC17. Indeed, these DHHC proteins promote stable membrane attachment of CSP, which is otherwise cytosolic. An inverse correlation was identified between membrane affinity of unpalmitoylated CSP mutants and subsequent palmitoylation: mutants with an increased membrane affinity localize to the endoplasmic reticulum (ER) and are physically separated from the Golgi-localized DHHC proteins. Palmitoylation of an ER-localized mutant could be rescued by brefeldin A treatment, which promotes the mixing of ER and Golgi membranes. Interestingly though, the palmitoylated mutant remained at the ER following brefeldin A washout and did not traffic to more distal membrane compartments. We propose that CSP has a weak membrane affinity that allows the protein to locate its partner Golgi-localized DHHC proteins directly by membrane "sampling." Mutations that enhance membrane association prevent sampling and lead to accumulation of CSP on cellular membranes such as the ER. The coupling of CSP palmitoylation to Golgi membranes may thus be an important requirement for subsequent sorting.
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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.