Rab10-KO Mouse

Rab10, a member of the small GTPase family, is involved in multiple cellular trafficking processes. It plays a role in the formation of recycling endosomal compartments like tubular endosomes through interaction with kinesin motors KIF13A and KIF13B [10]. Rab10 is also associated with pathways related to cell migration, lysosomal function, and is implicated in several disease conditions, making it a potential biomarker or drug target.

In Alzheimer's disease, a rare variant in the 3'-UTR of RAB10 has been identified as protective, indicating its possible role in disease resilience [2]. In Parkinson's disease, genetic variation at the LRRK2 locus, which can phosphorylate Rab10, is linked to disease risk. Lysosomal positioning regulates Rab10 phosphorylation by LRRK2, and loss of VPS13C, associated with early-onset Parkinson's disease, disrupts phospho-Rab10-mediated lysosomal function [4,5]. Also, urinary Rab10 phosphorylation is elevated in idiopathic Parkinson disease and is associated with disease progression [7]. In hepatocellular carcinoma, O-GlcNAcylation of RAB10 by OGT stabilizes it, accelerating cancer progression [3]. In breast cancer, RAB10 expression is elevated, promoting cell proliferation, migration, and invasion, and predicting a poor prognosis [9]. Moreover, Rab10-CAV1 mediated intraluminal vesicle transport to migrasomes is important for intercellular communication during skin wound healing [1]. Heterozygous Rab10 knock-out mice show changes in pathways related to neuronal metabolism, inflammation, and aging, and perform differently in hippocampal-dependent tasks, suggesting Rab10's role in controlling brain circuitry [6]. Rab10 also regulates lysosome exocytosis and plasma membrane repair [8].

In conclusion, Rab10 is crucial for multiple cellular functions such as endosomal formation, vesicle transport, and lysosomal function. Studies using gene knockout mouse models have revealed its significant roles in neurodegenerative diseases like Alzheimer's and Parkinson's, as well as in cancer. Understanding Rab10's functions provides insights into disease mechanisms and potential therapeutic targets.