Vps37d-KO Mouse

Vps37d, a component of the ESCRT-I complex, is crucial for multivesicular body formation and exosome biogenesis, processes involved in the traffic of molecules between cellular organelles [2]. It may play a role in pathways related to cell-cell interactions, as it has been associated with genes involved in neuronal development processes like cell adhesion, migration, growth, and cytoskeleton formation [1].

In a disabled boy with a complex chromosomal rearrangement t(5;7;21)dn, the Vps37d gene was disrupted, along with other genes involved in normal neuronal development. Although the disruption of TRIO was most likely the cause of the patient's MRD44-like phenotype, Vps37d may also cooperate in these key biological processes for neuronal development [1]. In corneal stromal cells from keratoconus patients, the mRNA of Vps37d was underexpressed, suggesting that disruptions in the exosome synthesis machinery, in which Vps37d is involved, may contribute to the altered molecular content of exosomes in keratoconus [2]. Frameshift mutations of Vps37d were found in gastric and colorectal cancers with high microsatellite instability, indicating that these alterations might contribute to the development of such cancers by deregulating vacuolar protein sorting proteins [3]. Also, pan-cancer analysis shows that the Vps37D gene has significant variation in breast cancer, predicting patient prognosis and being related to the tumor microenvironment, suggesting it could be a novel biomarker for early diagnosis and prognosis assessment [4].

In conclusion, Vps37d is important for exosome biogenesis and multivesicular body formation. Its disruption or abnormal expression is associated with neurodevelopmental disorders, keratoconus, and certain cancers. Studies on Vps37d contribute to understanding the mechanisms of these diseases and may provide potential diagnostic and prognostic markers.

References:

1. Córdova-Fletes, Carlos, Rivera, Horacio, Aguayo-Orozco, Thania Alejandra, Esparza-García, Eduardo, Domínguez-Quezada, Ma Guadalupe. 2022. A chromoanagenesis-driven ultra-complex t(5;7;21)dn truncates neurodevelopmental genes in a disabled boy as revealed by whole-genome sequencing. In European journal of medical genetics, 65, 104579. doi:10.1016/j.ejmg.2022.104579. https://pubmed.ncbi.nlm.nih.gov/35933106/

2. Blanco-Agudín, Noelia, Ye, Suhui, Alcalde, Ignacio, Merayo-Lloves, Jesús, Quirós, Luis M. 2025. Corneal stromal cells from patients with keratoconus exhibit alterations in the ESCRT-dependent machinery responsible for multivesicular body formation. In Experimental eye research, 252, 110260. doi:10.1016/j.exer.2025.110260. https://pubmed.ncbi.nlm.nih.gov/39890050/

3. An, Chang Hyeok, Kim, Yoo Ri, Kim, Ho Shik, Yoo, Nam Jin, Lee, Sug Hyung. 2011. Frameshift mutations of vacuolar protein sorting genes in gastric and colorectal cancers with microsatellite instability. In Human pathology, 43, 40-7. doi:10.1016/j.humpath.2010.03.015. https://pubmed.ncbi.nlm.nih.gov/21733561/

4. Chen, Xiao-Rui, Tan, Xue-Ying, Zhang, Zong-Liang, Yuan, Jiang-Shui, Song, Wei-Qing. 2025. ESCRT may function as a tumor biomarker, transitioning from pan-cancer analysis to validation within breast cancer. In Frontiers in immunology, 16, 1531940. doi:10.3389/fimmu.2025.1531940. https://pubmed.ncbi.nlm.nih.gov/40230849/