Vps53-flox Mouse

Vps53, a subunit of the Golgi-associated retrograde protein (GARP) complex, is involved in the retrograde pathway recycling endocytic vesicles to the Golgi. It also has a role in intracellular cholesterol transport and sphingolipid homeostasis in lysosomes [2,3]. The GARP complex, with Vps53 as part of it, is important for membrane-tethering in traffic from endosomes to the trans-Golgi network [5].

In colorectal cancer, Vps53 was found to be downregulated. Overexpression of Vps53 could suppress the proliferation, migration, and invasion of colorectal cancer cells, and accelerate apoptosis and autophagy. It was shown to upregulate Beclin 1 and LC3BII, suggesting its inductive effect on autophagy, and the autophagy inhibitor could attenuate the inhibition of Vps53 on colorectal cancer progression [1]. In a family with two affected siblings presenting with complicated hereditary spastic paraparesis, a homozygous pathogenic variant in Vps53 was identified, expanding the phenotype of Vps53-related disease [2]. Mutations in Vps53 were also found to cause progressive cerebello-cerebral atrophy type 2 in families of Jewish Moroccan ancestry [3]. A case of a neonate with Vps53 pathogenic variants presented with classic phenotypic features along with liver disease and deafness, suggesting liver involvement may be an under-recognized feature of Vps53-related pontocerebellar hypoplasia type 2E [4].

In conclusion, Vps53 is crucial for endosomal-Golgi trafficking and lipid homeostasis. Its dysregulation is associated with various neurodegenerative and cancer-related diseases. Studies on Vps53, especially those using genetic models to identify its role in different disease conditions, contribute to understanding the underlying disease mechanisms and may provide potential therapeutic targets for colorectal cancer, hereditary spastic paraparesis, progressive cerebello-cerebral atrophy, and pontocerebellar hypoplasia type 2E.