Variations in the configuration and behavior of microtubules within specific regions of the neuron serve as the basis for critical events in axonal and dendritic differentiation. Diseases of the nervous system are characterized by abnormal neuronal morphologies attributable to the improper configuration and malorientation of the microtubule array. Both mitotic and postmitotic cells employ molecular motor proteins to transport vital cargoes according to the needs of the cell, as well as to organize and reconfigure microtubules in response to environmental cues. Questions remain as to which motor proteins are responsible for engineering complex patterns of microtubule organization, and exactly how the balance of motor forces contributes to establishing the neuronal microtubule array. This application proposes to (1), use high resolution imaging to confirm that short microtubules are in transit down the axon (2), test the hypothesis that a small number of mitotic motor proteins are the key players in axonal microtubule transport and (3), determine whether different categories of microtubule transport have specific functional roles in axonal development in response to morphological guidance cues. ? ?
Myers, Kenneth A; Baas, Peter W (2007) Kinesin-5 regulates the growth of the axon by acting as a brake on its microtubule array. J Cell Biol 178:1081-91 |