Vps35-KO Mouse

Vps35, the vacuolar protein sorting-associated protein 35, is a core component of the retromer complex. It mediates intracellular protein transport, such as recycling receptors that mediate hydrolase transport to lysosomes [2,4,5]. Dysfunction of Vps35 is implicated in the accumulation of pathogenic proteins, and it is involved in multiple biological pathways and diseases, making it an important gene for functional studies [1].

In gastric cancer, Vps35 expression is upregulated. It promotes cell proliferation by recycling epidermal growth factor receptor (EGFR) to the cell surface, leading to the activation of the ERK1/2 pathway. High Vps35 expression also increases the sensitivity of gastric cancer models to EGFR inhibitors [1]. In another study on gastric cancer, Vps35 promotes tumour cell proliferation and metastasis through integrin-mediated activation of FAK-SRC kinases, inducing YAP activation and IL-6 expression. There is also a positive regulatory feedback loop between VPS35 and STAT3 [3].

In Parkinson's disease (PD), mutations in Vps35 (PARK17) cause a late-onset, autosomal dominant form. The D620N mutation in Vps35 can induce LRRK2 hyperactivation, impair endosomal recruitment of the WASH complex, and is linked to mitochondrial and autophagy-lysosomal pathway dysfunction [4].

In conclusion, Vps35 is essential for intracellular protein transport and endosomal sorting. Model-based research, especially in relation to diseases like gastric cancer and Parkinson's disease, has revealed its role in promoting cancer cell growth and in the pathophysiology of PD. Understanding Vps35 function may offer new therapeutic strategies for these diseases.