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. Delineation of a Reelin-Regulated Signaling Pathway to the Actin Cytoskeleton: Reelin is a secreted protein that initiates signaling cascades governing the proper positioning of neurons during vertebrate brain development. Genetic and biochemical data have identified a few signaling events that are very proximal to the engagement of Reelin with its cell surface receptors. However, it is presumed that Reelin's ability to properly position neurons ultimately requires Reelin signaling to regulate cytoskeletal changes that can alter cell mobility, cell structure and/or cell attachment. Using phosphoproteomic strategies a novel target of Reelin signaling has been identified that is a direct regulator of the actin cytoskeleton. This proposal aims to elucidate the molecular events that transduce this signal and to examine the cellular consequences on the actin cytoskeleton. The studies proposed are anticipated to take a year's time and will enable the submission of a more extensive proposal.