دورية أكاديمية
Endogenous Protein-Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex.
| العنوان: | Endogenous Protein-Protein Interaction Network of the NPC Cholesterol Transporter 1 in the Cerebral Cortex. |
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| المؤلفون: | Javanshad R; Department of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States., Nguyen TTA; Department of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States., Azaria RD; Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States., Li W; Department of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States., Edmison D; Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, Illinois 60612, United States., Gong LW; Department of Biological Sciences, University of Illinois Chicago, Chicago, Illinois 60607, United States., Gowrishankar S; Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, Illinois 60612, United States., Lieberman AP; Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States., Schultz ML; Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, United States., Cologna SM; Department of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607, United States. |
| المصدر: | Journal of proteome research [J Proteome Res] 2024 Aug 02; Vol. 23 (8), pp. 3174-3187. Date of Electronic Publication: 2024 Apr 30. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101128775 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-3907 (Electronic) Linking ISSN: 15353893 NLM ISO Abbreviation: J Proteome Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Chemical Society, c2002- |
| مواضيع طبية MeSH: | Cerebral Cortex*/metabolism , Niemann-Pick C1 Protein* , Protein Interaction Maps*, Animals ; Mice ; Humans ; Proteomics/methods ; Intracellular Signaling Peptides and Proteins/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Niemann-Pick Disease, Type C/metabolism ; Niemann-Pick Disease, Type C/genetics ; Mutation ; Mice, Knockout ; Cholesterol/metabolism ; Neurons/metabolism |
| مستخلص: | NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein-protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics. The current study investigated protein-protein interactions specific to the wild-type and the most prevalent NPC1 mutation (NPC1 I1061T ) while filtering out any protein interactor identified in the Npc1 -/- mouse model. Additionally, the results were matched across the two species to map the parallel interactome of wild-type and mutant NPC1 I1061T . Most of the identified wild-type NPC1 interactors were related to cytoskeleton organization, synaptic vesicle activity, and translation. We found many putative NPC1 interactors not previously reported, including two SCAR/WAVE complex proteins that regulate ARP 2/3 complex actin nucleation and multiple membrane proteins important for neuronal activity at synapse. Moreover, we identified proteins important in trafficking specific to wild-type and mutant NPC1 I1061T . Together, the findings are essential for a comprehensive understanding of NPC1 biological functions in addition to its classical role in sterol efflux. |
| فهرسة مساهمة: | Keywords: Interactome; Lysosomal Storage Disorder; Neurodegenerative Disease; Niemann-Pick type C; Transmembrane Protein |
| المشرفين على المادة: | 0 (Niemann-Pick C1 Protein) 0 (Intracellular Signaling Peptides and Proteins) 0 (Npc1 protein, mouse) 97C5T2UQ7J (Cholesterol) 0 (NPC1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240430 Date Completed: 20240802 Latest Revision: 20240802 |
| رمز التحديث: | 20240802 |
| DOI: | 10.1021/acs.jproteome.3c00788 |
| PMID: | 38686625 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1535-3907 |
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| DOI: | 10.1021/acs.jproteome.3c00788 |