{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARL8B is a conserved small GTPase that primarily localizes to lysosomal membranes and acts as a master regulator of lysosome positioning, trafficking, and fusion across diverse cellular contexts. By recruiting motor‐protein complexes in a microtubule‐dependent manner, ARL8B promotes centrifugal (anterograde) lysosome transport through interaction with its effector SKIP and the BORC complex, thereby enabling lysosome redistribution to the cell periphery in multiple cell types—including macrophages, dendritic cells, and natural killer cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " This localized positioning is critical for diverse biological functions, as ARL8B-dependent lysosome movement underpins immune responses by facilitating endocytic degradation and antigen presentation"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": ", and it supports proper presynaptic assembly by preventing premature aggregation of cargo during long‐distance axonal transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, ARL8B is pivotal for cell motility and invasion. Through its ability to control lysosome positioning, ARL8B regulates the secretion of lysosomal proteases and influences lipid metabolism, thereby contributing to extracellular matrix remodeling and promoting invasive tumor growth and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Concurrently, several intracellular pathogens, such as Salmonella enterica and misfolded prion proteins, subvert ARL8B-dependent trafficking pathways to manipulate the host endocytic network for successful intracellular survival or aggregation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these roles, post-translational modifications—in particular N-terminal acetylation—modulate ARL8B’s lysosomal targeting and function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", while ARL8B activity is further integrated with signaling pathways that adjust lysosomal morphology (e.g., tubulation in response to LPS via mTOR-dependent mechanisms)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": " Moreover, ARL8B contributes to directional vesicular transport processes such as the regulation of late endosome dynamics in cell migration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "and influences processes in specialized cells like melanocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Recent methodological advances have also enabled detailed characterization of ARL8B’s interacting partners and effectors—including its regulatory association with components like RNF167"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", SKIP"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ", and RUFY3"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "—further underscoring its multifaceted role in lysosomal dynamics. Collectively, these studies establish ARL8B as a central coordinator of lysosomal motility and membrane traffic, with broad implications for cellular homeostasis, immunity, pathogen-host interactions, and disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "27"}, {"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ARL8B functions as a critical integrator of lysosomal positioning and trafficking signals—governing the spatial dynamics of lysosomes to support endocytic degradation, antigen presentation, cell migration, and defense against pathogens, while also being implicated in tumor biology and neurodegeneration.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Irmgard Hofmann, Sean Munro "}, {"type": "b", "children": [{"type": "t", "text": "An N-terminally acetylated Arf-like GTPase is localised to lysosomes and affects their motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02958"}], "href": "https://doi.org/10.1242/jcs.02958"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16537643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16537643"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carlos M Guardia, Ginny G Farías, Rui Jia, et al. 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