Peptidergic granules in trigeminal ganglion neurons

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Description (provided by the applicant): Regulated secretion of neuropeptides is essential for maintaining homeostasis within the nervous system. This process relies on the proper assembly of peptide-containing large dense core vesicles (LDCVs, or secretory granules), which in turn requires coordinated machinery to synthesize the LDCV membrane, package soluble contents, and retrieve components for degradation or recycling. Although these trafficking events are critical to function, little is known regarding the biosynthetic or recycling pathways of LDCVs in neurons. The studies proposed will focus on the trafficking of peptidylglycine alpha-amidating monooxygenase (PAM), an integral granule membrane protein known to carry out the last steps in the peptide biosynthetic pathway. The cytosolic domain of PAM contains routing information and is phosphorylated by the kinase PCIP2 at Ser949. This proposal will specifically test the hypothesis that PAM-1 is a dynamic component of secretory membranes in peptidergic neurons of the trigeminal ganglion, and that specific trafficking steps are regulated by phosphorylation at Ser949 by P-CIP2.