Neurons extend two distinct types of neurites, axons, and dendrites. Axons are highly specialized to transmit information over long distances, whereas dendrites are highly specialized to receive and process information. A growing body of evidence indicates that the more overt differences between these neurites derive from underlying differences in their cytoskeletal structure, and in particular of their microtubules. Microtubules are filamentous proteins that have important functions in cellular architecture and motility. In recent years, considerable effort has been devoted toward understanding the regulation and functions of microtubules in the axon. In contrast, dendritic microtubules are poorly studied. The experiments in this application will explore the role of MAP-2, a somatodendritic-specific microtubule-associated protein in the organization and stability properties of dendritic microtubules. Other experiments will explore the potential role of microtubules in regulating organelle transport in the dendrite. These studies will resolve important issues about dendritic microtubules, and will thereby provide new insights into the mechanisms that generate and maintain neuronal polarity. Information of this kind is essential for understanding the cell biology of the neuron, and for elucidating the causes and potential cures for neuropathologies involving retardation of dendritic growth, and/or loss of neuronal polarity.
