P1-SPATIAL REGULATION OF PROTEIN KINASE A SIGNALING DURING GROWTH CONE GUIDANCE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在胚胎发育过程中，神经细胞（或神经元）必须从它们的起源点延伸到适当的目标，以形成神经系统的复杂，相互连接的网络。 引导从起点到目标的旅程是一组复杂的化学信号，这些信号引导神经元远离错误的目标并朝向正确的目标。 我们提出的工作将研究DCC（结直肠癌中的一种蛋白质，一些神经元表面的信号接收分子）和PKA（蛋白激酶A，细胞内的一种信号传递分子）的相互作用，以及这种相互作用对引导神经细胞到达正确目标的重要性。 我们最近的观察表明，这种相互作用是由Ezrin介导的，Ezrin是一种已知在细胞运动过程中将细胞膜与细胞内细胞骨架偶联的重要蛋白质。 我们提出的工作将进一步定义DCC，Ezrin和PKA之间的相互作用，在控制神经元寻路和血管系统的模式化的形态相似的过程。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During embryonic development, nerve cells (or neurons) must stretch from their point of origin to reach their proper target in order to form the intricate, interconnected network of the nervous system. Guiding the journey from origin to target is a complex set of chemical signals that steer neurons away from wrong targets and towards the correct ones. Our proposed work will investigate the interaction of DCC (Deleted in Colorectal Cancer, a signal-receiving molecule on the surface of some neurons) and PKA (Protein Kinase A, a signal-transmitting molecule inside cells) and the importance of this interaction for steering nerve cells to their proper target. Our recent observations suggest that this interaction is mediated by Ezrin, a protein known to be important in coupling the cell membrane to the intracellular cytoskeleton during cell movement. Our proposed work will further define the interplay between DCC, Ezrin, and PKA in controlling neuronal pathfinding and in the morphological similar process of patterning of the vascular system.