PP1 is a peptide derived from the the linker domain of synaptotagmin-11 (Syt11), which competitively inhibits the interaction of Syt11 with its direct binding proteins vps10p-tail-interactor-1a (vti1a) and vti1b. Synaptotagmin-11 is a non-Ca2+-binding Syt associated with Parkinsons disease and schizophrenia and Syt11 is the most abundantly expressed isoform of the Syt family in microglia, essential for brain development. Syt11 inhibits microglial activation in vivo and application of PP1 induces more cytokine secretion in wildtype microglia upon LPS treatment, phenocopying defects in Syt11 knockdown cells, consistent with the mechanism of regulation of cytokine release by Syt11 being mediated by its interactions with vti1a/vti1b.
