{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nResearch on the autoantigens IA‐2 and IA‐2β (phogrin) has shown that these dense‐core vesicle proteins play key roles in modulating insulin secretion and β‐cell function. Detailed genomic characterization and gene knockout studies in mice revealed that loss of IA‐2β results in mild glucose intolerance and impaired glucose‐stimulated insulin secretion, while combined deletion of IA‐2 and IA‐2β disrupts the first phase of insulin release and alters vesicle homeostasis, leading to multiple neuroendocrine and circadian disturbances. Moreover, studies examining the trafficking and recycling of phogrin—its sorting from the cell surface back into insulin‐containing granules and identification of DCV targeting motifs in its cytosolic domain—further underline its importance in secretory granule stability and β‐cell responsiveness. In addition, interactions between phogrin and the insulin receptor and protection of key signaling intermediates (such as IRS2) from degradation have been shown to support autocrine insulin signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies in related neuroendocrine systems underscore the broader context in which secretory vesicle proteins operate. For example, characterization of mouse Neuron navigator 1 (mNAV1) points to mechanisms of cytoskeletal association and directional migration in the developing nervous system, while investigations in osteoarthritis have identified functional voltage‐gated sodium channels (such as Nav1.7) in chondrocytes, implicating similar principles of regulated membrane trafficking in other tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin this complex regulatory network, microRNAs have emerged as critical post‐transcriptional modulators of autoantigen expression. In particular, bioinformatics and functional studies on the imprinted 14q32 miRNA cluster—which includes MIR1302‑10—demonstrate that several miRNAs are predicted to target and modulate the mRNA levels of key type 1 diabetes autoantigens, including IA‐2 and IA‐2β. Although the broader impact of these miRNAs on β‐cell function and insulin secretion is still being unraveled, the data indicate that MIR1302‑10 may contribute to fine‐tuning the levels of these autoantigens, thereby influencing secretory dynamics and autoimmunity in diabetes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Atsutaka Kubosaki, Steffen Gross, Junnosuke Miura, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "An extended tyrosine-targeting motif for endocytosis and recycling of the dense-core vesicle membrane protein phogrin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2005.00292.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2005.00292.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15882444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15882444"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Atsutaka Kubosaki, Shinichiro Nakamura, Abner Louis Notkins "}, {"type": "b", "children": [{"type": "t", "text": "Dense core vesicle proteins IA-2 and IA-2beta: metabolic alterations in double knockout mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/diabetes.54.suppl_2.s46"}], "href": "https://doi.org/10.2337/diabetes.54.suppl_2.s46"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16306340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16306340"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Asako Doi, Takeshi Shono, Masahiro Nishi, et al. 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