Abstract of project The human brain is a flexible structure that changes in response to experiences but it is not fully understood how experience changes the brain at the cellular level and results in learning and memory. The question posed in this proposal is "what is the role of the actin-dependent molecular motor, brain myosin5, in experience-driven synaptic plasticity, i.e how does myosin5 participate in synaptic strengthening?" Brain myosin5 (Myosin-Va) has multiple functions that link it to synaptic plasticity. It transports vesicles as well as other kinds of cargo at axon terminals and dendritic spines. In addition, it is a constitutive component of the postsynaptic density. Previous studies have shown that myosin5 binds to kinesin (heteromotor complex) and functions as a molecular motor for the transport of endoplasmic reticulum (ER) vesicles. Those studies led to the following specific question to be addressed in this project: How is transport of ER vesicles by myosin5 and kinesin coordinated. The specific aims are as follows: The PI and his research group will isolate brain-specific binding partners of myosin5 using affinity-based biochemical methods and identify the proteins using proteomic approaches (brain-specific myosin5 proteome). The results from this proteomics screen will be used to determine which proteins constitute the myosin5/kinesin heteromotor complex. From the list of proteins identified by proteomics, they will identify signaling proteins that associate with the myosin5/kinesin motor complex and determine which of these signaling proteins function to coordinate kinesin and myosin5 activity during transport of ER vesicles using an in vitro motility assay.
Broader impacts resulting from the proposed activities: The broader impacts will include mentoring by the PI of minority students through the Ernest Everett Just Program at Dartmouth, sponsoring undergraduate students engaged in independent research projects and honor's theses research in his laboratory and working with students from Spelman College and Morehouse College (2 HBCUs) who come to Dartmouth as exchange students. In addition, the PI will continue to sponsor undergraduate students in his laboratory at the Marine Biological Laboratory, Woods Hole MA. Each summer he gives lectures on his research and provides mentoring to minority graduate students enrolled in the SPINES (Neuro) course at the MBL.
