Peptidergic granules in trigeminal ganglion neurons

描述(由申请人提供)：神经肽的调节分泌对于维持神经系统内的动态平衡是必不可少的。这一过程依赖于含有多肽的大型致密核心囊泡(LDCV或分泌颗粒)的正确组装，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，并回收用于降解或回收的成分。尽管这些转运事件对功能至关重要，但人们对LDCV在神经元中的生物合成或循环途径知之甚少。拟议的研究将集中在多肽甘氨酸α-酰胺化单加氧酶(PAM)的运输上，PAM是一种完整的颗粒膜蛋白，负责多肽生物合成途径的最后几步。PAM的胞液结构域包含路由信息，并被Ser949的PCIP2激酶磷酸化。这一提议将专门检验这样的假设，即PAM-1是三叉神经节肽能神经元分泌膜的动态成分，并且特定的转运步骤受P-CIP2在Ser949处的磷酸化调控。

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.