Peptidergic granules in trigeminal ganglion neurons

描述（由申请人提供）：调节神经肽的分泌对维持神经系统内的稳态至关重要。这一过程依赖于含有多肽的大致密核心囊泡（LDCV，或分泌颗粒）的适当组装，这反过来又需要协调的机器来合成LDCV膜，包装可溶性内容物，并回收降解或回收成分。尽管这些转运事件对神经元的功能至关重要，但对于神经元中LDCVs的生物合成或再循环途径知之甚少。提出的研究将集中在肽酰甘氨酸α -酰胺化单加氧酶（PAM）的运输上，这是一种完整的颗粒膜蛋白，已知在肽生物合成途径中执行最后步骤。PAM的胞质结构域包含路线信息，并在Ser949位点被PCIP2激酶磷酸化。该提案将专门验证PAM-1是三叉神经节肽能神经元分泌膜的动态成分的假设，并且特定的运输步骤由P-CIP2在Ser949位点磷酸化调节。

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.