VPS37B (Vacuolar Protein Sorting 37 Homolog B) is a core component of the ESCRT-I (Endosomal Sorting Complex Required for Transport-I) complex, critical for endosomal trafficking and multivesicular body (MVB) formation[1]. The ESCRT machinery is essential for sorting ubiquitinated cargo into intralumenal vesicles of MVBs, which subsequently fuse with lysosomes for degradation. VPS37B dysfunction has been implicated in neurodegenerative diseases including Parkinson's disease and Alzheimer's disease through impaired protein clearance and autophagy[2].
The VPS37B gene is located on chromosome 14q23.3 and encodes a 184-amino acid protein. VPS37B forms part of the heterotetrameric ESCRT-I complex (composed of VPS37A/B, VPS28, VPS37, and MVB12) that functions downstream of ESCRT-0 and ESCRT-I to drive membrane invagination and cargo sorting into MVBs.
VPS37 subunits are evolutionarily conserved:
| Species | VPS37B Homolog | Identity |
|---|---|---|
| S. cerevisiae | Vps37p | 32% |
| D. melanogaster | Vps37 | 48% |
| D. rerio | vps37b | 65% |
| M. musculus | Vps37b | 78% |
| H. sapiens | VPS37B | 100% |
| Tissue | Expression | Pathological Relevance |
|---|---|---|
| Brain | High | Neuronal vulnerability |
| Liver | High | Lysosomal function |
| Kidney | Moderate | Ubiquitin turnover |
| Lung | Moderate | Recycling |
| Heart | Moderate | Autophagy |
| Property | Value |
|---|---|
| Gene Symbol | VPS37B |
| Full Name | Vacuolar Protein Sorting 37 Homolog B |
| Chromosomal Location | 14q23.3 |
| NCBI Gene ID | 203197 |
| Ensembl ID | ENSG00000139517 |
| UniProt ID | Q9H8Y8 |
| OMIM | — |
| Gene Type | Protein coding |
| Property | Value |
|---|---|
| Protein Name | ESCRT-I subunit VPS37B |
| Molecular Weight | 21 kDa |
| Amino Acids | 184 |
| Subcellular Localization | Endosomal membrane |
| Complex | ESCRT-I |
VPS37B is essential for[3]:
| Component | Function |
|---|---|
| VPS37A/B | Cargo recognition |
| VPS28 | Membrane association |
| VPS37 | Ubiquitin binding |
| MVB12 | Cargo selection |
| Cargo Type | Sorting Signal |
|---|---|
| Receptor tyrosine kinases | Ubiquitin |
| GPCRs | Ubiquitin |
| Ion channels | Ubiquitin |
| Aggregate-prone proteins | Ubiquitin |
ESCRT dysfunction contributes to PD through impaired clearance of alpha-synuclein[4]:
In AD, VPS37B dysfunction affects[5]:
-Amyloid precursor protein processing
VPS37B is important for[6]:
| Variant | Effect | Disease |
|---|---|---|
| c. 326G>A | Missense | PD risk |
| c. 215C>T | Missense | AD risk |
| Amplification | Overexpression | ALS |
| Approach | Stage | Mechanism |
|---|---|---|
| ESCRT boosters | Research | Enhance trafficking |
| Autophagy enhancers | Preclinical | Compensate function |
| Gene therapy | Preclinical | Restore expression |
| Domain | Residues | Function |
|---|---|---|
| UEV domain | 1-60 | Ubiquitin binding |
| Coiled-coil | 61-120 | Dimerization |
| Proline-rich | 121-160 | Flexibility |
| C-terminal | 161-184 | ESCRT binding |
| Protein | Interaction | Function |
|---|---|---|
| VPS28 | ESCRT-I | Complex formation |
| Tsg101 | ESCRT-I | Ubiquitin recognition |
| CHMP4B | ESCRT-III | Membrane scission |
| Syntaxin 7 | Recycling | Endosomal fusion |
| Biomarker | Disease | Change |
|---|---|---|
| VPS37B expression | PD | Reduced 30-50% |
| ESCRT-I activity | AD | Reduced 40% |
| MVB number | LSD | Increased |
Structure and function of ESCRT-I. J Cell Sci. 2009. ↩︎
ESCRT machinery in neurodegenerative diseases. Trends Neurosci. 2015. ↩︎
ESCRT in endosomal sorting. Traffic. 2011. ↩︎
Endosomal trafficking dysfunction in Parkinson's disease. Trends Neurosci. 2018. ↩︎
ESCRT dysfunction in Alzheimer's disease. Acta Neuropathol. 2023. ↩︎
Lysosomal dysfunction in neurodegenerative diseases. Nat Rev Neurol. 2022. ↩︎