Peptidergic granules in trigeminal ganglion neurons

描述（由申请方提供）：调节神经肽的分泌对于维持神经系统内的稳态至关重要。该过程依赖于含肽的大致密核心囊泡（LDCV或分泌颗粒）的适当组装，这又需要协调的机械来合成LDCV膜、包装可溶性内容物并回收用于降解或再循环的组分。虽然这些贩运事件是至关重要的功能，很少有人知道的生物合成或回收途径的LDCV在神经元。拟议的研究将集中在运输的肽酰甘氨酸α-酰胺化单加氧酶（PAM），一个完整的颗粒膜蛋白进行肽生物合成途径中的最后一步。PAM的胞质结构域包含路由信息，并被激酶PCIP 2在Ser 949处磷酸化。该提议将具体地测试PAM-1是三叉神经节的肽能神经元中的分泌膜的动态组分，并且特定的运输步骤由P-CIP 2在Ser 949处的磷酸化调节的假设。

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.