{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRab10 is a multifaceted small GTPase that plays central roles in intracellular membrane trafficking and organelle dynamics. It regulates the structure and dynamics of the endoplasmic reticulum by localizing to specialized domains that mark sites of new tubule growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, Rab10 associates with key cargo‐sorting machineries such as myosin V isoforms to direct endocytic vesicle trafficking"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", participates in insulin‐stimulated GLUT4 translocation by triggering the movement and fusion of GLUT4‐laden vesicles"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and contributes to the biogenesis of tubular recycling endosomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, during pathogen internalization, Rab10 transiently associates with early phagosomes to facilitate their maturation into phagolysosomes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while it is also involved in regulating the trafficking of hyaluronan synthase through the control of its retrograde transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "Rab10 also emerges as a critical mediator in neurodegenerative signaling and cellular quality control. In models of Parkinson’s disease, depolarized mitochondria accumulate Rab10 in a manner dependent on PINK1 and parkin, promoting the recruitment of autophagy receptors such as OPTN and facilitating mitophagy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Its phosphorylation by pathogenic forms of LRRK2 is associated with defects in centrosomal cohesion and ciliogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and quantitative assays in peripheral blood have exploited phospho‐Rab10 as a readout of hyperactive LRRK2 kinase signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Altered Rab10 phosphorylation patterns have also been documented in Alzheimer’s disease tissue, linking aberrant vesicular trafficking to neurodegeneration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", while additional LRRK2–Rab10 studies support its role in modulating endolysosomal and presynaptic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "12"}]}, {"type": "t", "text": "In the context of cancer, Rab10 has been implicated as an oncogenic driver and as a target of diverse noncoding RNAs that dictate tumor progression. In hepatocellular carcinoma, elevated Rab10 levels promote cell survival and proliferation by orchestrating multiple signaling cascades"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", and its stability can be enhanced through O-GlcNAcylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Rab10 is also subject to post-transcriptional regulation in various malignancies: in osteosarcoma, both miR-329 and the long noncoding RNA EBLN3P act to suppress Rab10 expression and thereby inhibit tumorigenicity"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": "; in gastric cancer, circ_0001658 promotes oncogenic cell proliferation via a miR-182/Rab10 axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "; and in esophageal squamous cell carcinoma, circUBAP2 facilitates tumor progression by sponging miR-422a to upregulate Rab10."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Moreover, in glioma, dysregulated levels of the lncRNA PSMB8-AS1 drive proliferation by modulating a miR-574-5p/Rab10 signaling cascade"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", while in ovarian cancer, miR-409-3p targets Rab10 to suppress cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " In hepatocellular carcinoma, additional studies have reported that miR-557-mediated inhibition of Rab10 curbs malignant behaviors"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", and in acute myeloid leukemia, a miR-106b-5p/Rab10 axis has been proposed as a promising diagnostic and prognostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "23"}]}, {"type": "t", "text": "Additional functions of Rab10 expand its influence to developmental and host–pathogen processes. During spermiogenesis, Rab10 forms complexes with the testis-restricted regulator MGCRABGAP and localizes to the manchette to facilitate proper sperm head formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": " In the battle against intracellular pathogens, the Salmonella virulence factor SopD selectively binds and inhibits Rab10 to promote plasma membrane scission and successful vacuole formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": " Together, the diverse evidence—including studies linking Rab10 to endolysosomal trafficking and presynaptic functions"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "—establishes Rab10 as a critical integrator of membrane dynamics in both physiological and pathological settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "Overall, Rab10 serves as a versatile regulator whose impact spans from the control of intracellular traffic and vesicle recycling to the modulation of cellular responses in neurodegeneration, oncogenesis, and host defense. 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