Axonal growth depends on the delivery of newly synthesized plasma membrane and cytoskeletal components from the cell body to the axon. These components are conveyed by various forms of transport along axonal microtubules (MTs). The formation and maintenance of the MTs, in turn, requires incorporation of new tubulin, the structural subunit of MTs, into the MT array. Tubulin is transported from the cell body to the axon by slow axonal transport at a rate of a few mm/day. Although the mechanism of slow axonal transport is not yet known, it is generally believed that this transport is supported by a population of stationary MTs. Our recent data indicate that the pattern of MT movement in developing nerve processes is much more complex than previously anticipated. Specifically, in different culture conditions, MTs in the axonal shaft are transported en bloc anterogradely (to the growth cone), retrogradely (to the soma), or remain stationary relative to the substrate. The observed vectorial flux of axonal MTs reflects the activity of mechanical forces exerted on the MT array. The cellular mechanisms for the generation of such forces are not known. Our overall objective in the proposed research project is to elucidate the mechanism of MT translocation in growing neurites and to establish relationship between MT movement and axonal growth. The approach will be to directly measure the rates of MT transport in developing nerve processes using a combination of digital fluorescence microscopy and photobleaching techniques. Our studies will resolve the long-standing controversy regarding the mode of tubulin transport in growing axons. Determining the mechanisms of MT transport is important not only for understanding the process of axonal growth but also for the design of new therapeutic strategies aimed at prevention and treatment of neurological diseases.
| Samsonov, Andrey; Yu, Jiang-Zhou; Rasenick, Mark et al. (2004) Tau interaction with microtubules in vivo. J Cell Sci 117:6129-41 |
| Ma, Yitao; Shakiryanova, Dinara; Vardya, Irina et al. (2004) Quantitative analysis of microtubule transport in growing nerve processes. Curr Biol 14:725-30 |
