ArticleThe Journal of biological chemistry2013
In silico screening for palmitoyl substrates reveals a role for DHHC1/3/10 (zDHHC1/3/11)-mediated neurochondrin palmitoylation in its targeting to Rab5-positive endosomes.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Dissociation of Golgi-associated DHHC-type Zinc Finger Protein (GODZ)- and Sertoli Cell Gene with a Zinc Finger Domain-β (SERZ-β)-mediated Palmitoylation by Loss of Function Analyses in Knock-out Mice.The Journal of biological chemistry · 2016Guideline
- ASCT2 palmitoylation regulated by JNK1-ZDHHC14 axis orchestrates glutamine metabolism and NSCLC progression.Cell discovery · 2026Article
- Temporal and protein-specific S-palmitoylation supports synaptic and neural network plasticity.Cellular and molecular life sciences : CMLS · 2025Article
- Palmitoylation and regulation of potassium-dependent sodium/calcium exchangers (NCKX).Bioscience reports · 2025Article
- Palmitoylation in cancer: decoding its roles in signal transduction, tumor immunity, and emerging therapeutic opportunities.Frontiers in immunology · 2025Review
- Palmitoylation of synaptic proteins: roles in functional regulation and pathogenesis of neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
- S-acylation of Ca2+ transport proteins: molecular basis and functional consequences.Biochemical Society transactions · 2024Review
- Article
- Functions and mechanisms of the GPCR adaptor protein Norbin.Biochemical Society transactions · 2023Review
- A high-affinity cocaine binding site associated with the brain acid soluble protein 1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Function of SYDE C2-RhoGAP family as signaling hubs for neuronal development deduced by computational analysis.Scientific reports · 2022Article
- The GPCR adaptor protein norbin suppresses the neutrophil-mediated immunity of mice to pneumococcal infection.Blood advances · 2021Article
- Protein S-Palmitoylation and Lung Diseases.Advances in experimental medicine and biology · 2021Article
- The palmitoyl acyltransferases ZDHHC5 and ZDHHC8 are uniquely present in DRG axons and control retrograde signaling via the Gp130/JAK/STAT3 pathway.The Journal of biological chemistry · 2020Article
- Role of Palmitoylation of Postsynaptic Proteins in Promoting Synaptic Plasticity.Frontiers in molecular neuroscience · 2019Review
- Neurochondrin interacts with the SMN protein suggesting a novel mechanism for spinal muscular atrophy pathology.Journal of cell science · 2018Article
- Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies.Chemical reviews · 2018Article
- Methotrexate combined with methylprednisolone for the recovery of motor function and differential gene expression in rats with spinal cord injury.Neural regeneration research · 2017Article
- Article
- ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation.Molecular and cellular biology · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein palmitoylation, a common post-translational lipid modification, plays an important role in protein trafficking and functions. Recently developed palmitoyl-proteomic methods identified many novel substrates. However, the whole picture of palmitoyl substrates has not been clarified. Here, we performed global in silico screening using the CSS-Palm 2.0 program, free software for prediction of palmitoylation sites, and selected 17 candidates as novel palmitoyl substrates. Of the 17 candidates, 10 proteins, including 6 synaptic proteins (Syd-1, transmembrane AMPA receptor regulatory protein (TARP) γ-2, TARP γ-8, cornichon-2, Ca(2+)/calmodulin-dependent protein kinase IIα, and neurochondrin (Ncdn)/norbin), one focal adhesion protein (zyxin), two ion channels (TRPM8 and TRPC1), and one G-protein-coupled receptor (orexin 2 receptor), were palmitoylated. Using the DHHC palmitoylating enzyme library, we found that all tested substrates were palmitoylated by the Golgi-localized DHHC3/7 subfamily. Ncdn, a regulator for neurite outgrowth and synaptic plasticity, was robustly palmitoylated by the DHHC1/10 (zDHHC1/11; z1/11) subfamily, whose substrate has not yet been reported. As predicted by CSS-Palm 2.0, Cys-3 and Cys-4 are the palmitoylation sites for Ncdn. Ncdn was specifically localized in somato-dendritic regions, not in the axon of rat cultured neurons. Stimulated emission depletion microscopy revealed that Ncdn was localized to Rab5-positive early endosomes in a palmitoylation-dependent manner, where DHHC1/10 (z1/11) were also distributed. Knockdown of DHHC1, -3, or -10 (z11) resulted in the loss of Ncdn from Rab5-positive endosomes. Thus, through in silico screening, we demonstrate that Ncdn and the DHHC1/10 (z1/11) and DHHC3/7 subfamilies are novel palmitoyl substrate-enzyme pairs and that Ncdn palmitoylation plays an essential role in its specific endosomal targeting.
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