{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSynaptotagmin‐11 (Syt11) is emerging as a critical regulator of vesicular trafficking in immune cells and glia. In macrophages, Syt11 localizes to recycling endosomes and lysosomes where it modulates cytokine secretion and particle uptake, and its manipulation can either potentiate or suppress inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, Syt11’s C2 domains engage with components of the RNA‐induced silencing complex, suggesting a potential link between microRNA‐mediated gene regulation and membrane traffic."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In pathogenic settings, Syt11 is a target of degradation by a zinc metalloprotease, a process that alters cytokine output during infection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, in astrocytes Syt11 governs lysosome exocytosis that is essential for rapid cell membrane repair following injury"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while in microglia its expression restrains cytokine release and phagocytosis, thereby curbing excessive inflammatory activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neurons, Syt11 is found on abundant vesicles that differ from conventional synaptic vesicles, being more akin to trafficking endosomes that recycle in an activity‐dependent, yet slow and desynchronized, manner. This vesicular pool is critical for sustaining life and for supporting long‐term synaptic plasticity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, the proteolytic turnover of Syt11 is tightly regulated by the ubiquitin–proteasome system, a control mechanism that differs between neurons and astrocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Palmitoylation of Syt11 enhances its stability and increases its abundance on intracellular membranes, a modification that in turn promotes the binding of α‑synuclein and shifts its equilibrium toward an aggregation‑prone monomeric state, thereby linking Syt11 to the pathogenesis of Parkinson’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, Syt11 directly interacts with endophilin A1 via its C2B domain to inhibit excessive synaptic vesicle endocytosis, ensuring proper retrieval and partitioning of synaptic proteins during neurotransmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementing its roles in neurons, in vivo studies in microglia underscore Syt11’s function as a gatekeeper of immune responsiveness; targeted ablation in microglia leads to heightened inflammatory cytokine production and altered phagocytic activity, an effect mediated in part by direct binding to vti1a/vti1b."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, Syt11 acts as a vesicular scaffold in neurons by recruiting and stabilizing GABAB receptors together with Cav2.2 channels within post‑Golgi vesicles, thereby facilitating the assembly of presynaptic signaling complexes that are essential for regulated neurotransmitter release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Guillermo Arango Duque, Mitsunori Fukuda, Albert Descoteaux "}, {"type": "b", "children": [{"type": "t", "text": "Synaptotagmin XI regulates phagocytosis and cytokine secretion in macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1202500"}], "href": "https://doi.org/10.4049/jimmunol.1202500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23303671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23303671"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alexandra Milochau, Valérie Lagrée, Marie-Noëlle Benassy, et al. 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