PROJECT ABSTRACT
Microtubules are protein polymers that are essential for neuronal cell morphogenesis during
development. Microtubule assembly and function rely on the regulation of lattice-bound microtubule-associated
proteins (MAPs). Many known MAPs influence microtubule stability and organelle transport, and some of them
are highly associated with neurodegeneration. The proposed study will investigate a unique family of MAPs
that interact with both microtubules and the motor protein kinesin-1. Our recent study of its founding member
MAP7 provides the first demonstration of the neuronal function of this less-well understood MAP. MAP7 is
developmentally regulated to promote axonal branch formation of sensory neurons in the dorsal root ganglion
(DRG). Using primary neuronal cell culture, we have found that MAP7 regulates branch formation and growth.
Further cell biological analysis has revealed that MAP7 regulates microtubule stability and kinesin-1-mediated
organelle transport, two processes that are critical to axonal morphogenesis and function. Recently, we expand
our studies in several directions. First, we analyzed another MAP7D1, a closest MAP7 homolog and found that
it has similar properties and redundant function as MAP7 in culture. Second, we developed a new assay to
show the potential role of MAP7 in regulating transport during branch growth. Third, in the study of MAP7
mouse mutants, we found a potential new role of MAP7 in nociception. Following these findings, we
hypothesize that the MAP7 family proteins provide a novel mechanism and play multiple roles in axonal branch
development and function by regulating organelle transport. To test this hypothesis, we ask three questions: 1)
Are both MAP7/MAP7D1 required for branch development of DRG neurons? 2) How does MAP7 regulate
organelle transport for branch growth and nociception? 3) is the nociception function specific for MAP7
expressed in DRG neurons and its interaction with kinesin-1? Answering these questions will not only expand
our knowledge of this novel family of MAPs but also address fundamental questions regarding microtubule-
based intracellular transport in neuronal development and function. More importantly, our proposed studies
with a focus on DRG sensory neurons will allow us to explore the role of transport regulation in nociception and
thus bring us closer to medically relevant problems, such as pain. Given the importance of nociception and
pain in human health, our proposed studies with a focus on a fundamental cell biological problem are thus
highly relevant to the NIH mission of investigating brain functions and disorders.
