Synaptotagmin ‐11 regulates immune functions of microglia in vivo

Membrane trafficking pathways play crucial roles in microglial immune responses. However, the molecular mechanisms underlying these processes remain largely elusive. Here, we reported that synaptotagmin-11 (Syt11), an abundant Syt isoform in the brain that is associated with Parkinson's disease and schizophrenia, regulated microglial migration, cytokine release, and phagocytosis in the mouse brain. Further investigation discovered that Syt11 inhibited cytokine release via direct interactions with vps10p-tail-interactor-1a (vti1a) and vti1b. Our study reveals a novel inhibitory mechanism of microglia-mediated inflammation, which may provide potential therapeutic targets for the treatment of chronic neuroinflammation in aging and brain diseases. AbstractMembrane trafficking pathways mediate key microglial activities such as cell migration, cytokine secretion, and phagocytosis. However, the underlying molecular mechanism remains poorly understood. Previously, we found that synaptotagmin-11 (Syt11), a non-Ca2+-binding Syt associated with Parkinson's disease (PD) and schizophrenia, inhibits cytokine release and phagocytosis in primary microglia. Here we reported the in  vivo function of Syt11 in microglial immune responses using an inducible microglia-specific Syt11-conditional-knockout (cKO) mouse strain. Syt11-cKO resulted in activation of microglia and elevated mRNA levels of IL-6, TNF-α, IL-1β, and iNOS in various brain regions under both resting state and LPS-induced acute...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research