Structure And Function Of Cytoplasmic Motors

Neurological Disorders And Stroke

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Abstract

Delivery to nerve terminals of cytoskeletal proteins synthesized in the cell body is crucial for growth, maintenance and regeneration of neurons. Despite its importance, little is known about what motors are responsible for slow transport or in what forms these proteins are transported. We have shown that tubulin moves down the squid giant axon as an unpolymerized protein by both diffusion and slow axonal transport. Additionally, it appears as if the soluble motor that transports tubulin is loosely coupled to its cargo, since separation of the axon from the cell body leads to the rapid loss of slow transport, but not tubulin. To test this hypothesis directly, we are now measuring the binding coefficients of proteins within the transported complex. We have also developed a new 2-photon technique for studying slow transport by selectively disrupting individual cytoskeletal tracts. Moreover, we have shown that myosin, one of the candidate motors for slow transport, is also responsible for the purse-string constriction of the axon following transection. Finally, we have sequenced and characterized a number of the different myosins in the squid giant axon, and are now developing antibodies to determine the functional role of myosins in slow axonal transport.