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

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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.