ARL8B

Description

The ARL8B (ADP ribosylation factor like GTPase 8B) is a protein-coding gene located on chromosome 3.

ADP-ribosylation factor-like protein 8B is a protein that in humans is encoded by the ARL8B gene.

ARL8B is a small GTPase that cycles between an active GTP-bound state and an inactive GDP-bound state. In its active state, it binds to various effector proteins, playing a crucial role in regulating lysosomal positioning. This regulation is important for nutrient sensing, natural killer cell-mediated cytotoxicity, and antigen presentation. ARL8B, along with its effectors, orchestrates lysosomal transport and fusion. It specifically localizes to lysosomal membranes and mediates anterograde lysosomal motility by recruiting PLEKHM2, which in turn recruits the motor protein kinesin-1 on lysosomes. ARL8B is required for lysosomal and cytolytic granule exocytosis. It is a critical factor in NK cell-mediated cytotoxicity, driving the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. In neurons, ARL8B mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles, essential for presynaptic biogenesis and synaptic function. It also acts as a regulator of endosome to lysosome trafficking pathways, which is particularly important for host defense. ARL8B regulates cargo trafficking to lysosomes by binding to PLEKHM1 and recruiting the HOPS subunit VPS41, resulting in the functional assembly of the HOPS complex on lysosomal membranes. This plays a significant role in cargo delivery to lysosomes for antigen presentation and microbial killing. ARL8B directs the intersection of CD1d with lipid antigens in lysosomes and facilitates the intersection of phagosomes with lysosomes to generate phagolysosomes that kill microbes. It is involved in the process of MHC II presentation, regulating the delivery of antigens to lysosomes and the formation of MHC II-peptide complexes through the recruitment of the HOPS complex to lysosomes, enabling the fusion of late endosomes to lysosomes. ARL8B may also play a role in chromosome segregation.

ARL8B is also known as ARL10C, Gie1.

Associated Diseases

WES Whole Exome Sequencing