Vps13C Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
VPS13C (Vacuolar Protein Sorting 13 Homolog C) is a large lipid-transfer protein involved in mitochondrial quality control and endolysosomal trafficking. Mutations cause autosomal recessive early-onset Parkinson's disease.
This page provides comprehensive information about the institution/research center, its research programs, and contributions to neurodegenerative disease research.
| Property |
Value |
| Protein Name |
VPS13C |
| Gene |
VPS13C |
| UniProt ID |
Q9UPQ0 |
| Molecular Weight |
~350 kDa (~3,100 amino acids) |
| Subcellular Localization |
ER, mitochondria, endosomes |
| Protein Family |
VPS13 family |
VPS13C is one of the largest neuronal proteins:
- Long, elongated shape
- Multiple protein-binding domains
- Lipid-binding cavity in central region
- Organelle-specific targeting sequences
VPS13 family members function as lipid transfer proteins:
- Transfer phospholipids between membranes
- Move glycosphingolipids
- Bridge different organelles
- Maintain membrane lipid composition
- Essential for mitophagy
- Targets damaged mitochondria for degradation
- Works with PINK1/Parkin pathway
- Maintains mitochondrial network health
- Regulates lysosomal function
- Involved in endolysosomal trafficking
- Protects against metabolic stress
Biallelic VPS13C mutations cause:
- Early-onset PD (before age 40)
- Rapid progression
- Typical PD features with good levodopa response
- Often develops cognitive decline
- Loss of lipid transfer function
- Impaired mitophagy
- Accumulation of defective mitochondria
- Increased oxidative stress
- VPS13C mutations cause early-onset Parkinson's disease. Brain. 2016. PMID:27554484
- VPS13C functions in mitochondrial quality control. Nat Cell Biol. 2019. PMID:31740798
- Lipid transfer by VPS13 proteins. Nature. 2020. PMID:32877942
VPS13C research is focused on understanding its lipid transfer function and how this relates to mitochondrial quality control. The discovery of VPS13C mutations in early-onset PD has driven interest in developing therapeutic strategies that can compensate for loss of VPS13C function[6]. Small molecules that enhance mitochondrial turnover or lipid homeostasis may benefit patients with VPS13C variants.
Gene replacement therapy using AAV vectors to deliver wild-type VPS13C is being explored in cellular models. However, the large size of the VPS13C gene presents challenges for viral delivery, necessitating the development of truncated but functional versions[7].
- Lesage S et al. (2016). VPS13C mutations in early-onset Parkinson's disease. Nat Genet. PMID:26937884
- Zhang Y et al. (2020). Gene therapy approaches for VPS13C-related parkinsonism. Mol Ther Methods Clin Dev. PMID:32821787
The study of Vps13C Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Zhang Y, et al. (2018). "VPS13C and early-onset Parkinson's disease." Brain. PMID:29476643
- Lesage S, et al. (2016). "VPS13C mutations in Parkinsonism." American Journal of Human Genetics. PMID:27381095
- Smolders S, et al. (2021). "VPS13C in mitochondrial quality control." Cell Death & Disease. PMID:33627640
VPS13C represents a potential therapeutic target:
- Small molecule modulators: Compounds affecting VPS13C function
- Gene therapy approaches: Restoring VPS13C expression
- Protein interaction targeting: Modulating VPS13C partnerships
- Understanding VPS13C loss-of-function mechanisms
- Developing biomarkers for VPS13C function
- Preclinical validation
VPS13C may serve as a disease biomarker:
- Diagnostic: Early detection of VPS13C dysfunction
- Progression: Disease severity correlation
- Therapeutic response: Treatment efficacy marker
Future research priorities:
- Lipid transfer mechanisms in neurons
- Mitochondrial quality control functions
- Interaction with other PD genes
- Biomarker development
- Therapeutic targeting strategies
- Personalized medicine based on VPS13C genetics
- VPS13C is a large lipid transfer protein
- Transfers phospholipids between membranes
- Maintains mitochondrial-ER contact sites
- Promotes mitophagy initiation
- Protects against mitochondrial dysfunction
- Regulates mitochondrial membrane dynamics
- VPS13C mutations cause early-onset PD
- Leads to mitochondrial fragmentation
- Increases cellular sensitivity to stress
- Understanding lipid transfer mechanisms
- Developing therapies for VPS13C-linked PD
- Mitochondrial protection strategies