Distinct cytoplasmic dynein complexes are transported by different mechanisms in axons

摘要

In neurons, cytoplasmic dynein is synthesized in the cell body, but its function is to move cargo from the axon back to the cell body. Dynein must therefore be delivered to the axon and its motor activity must be regulated during axonal transport. Cytoplasmic dynein is a large protein complex composed of a number of different subunits. The dynein heavy chains contain the motor domains and the intermediate chains are involved in binding the complex to cargo. Five different intermediate chain polypeptides, which are the result of the alternative splicing of the two intermediate chain genes, have been identified. We have characterized two distinct pools dynein that are transported from the cell body along the axon by different mechanisms. One pool, which contains the ubiquitous intermediate chain, is associated with the membranous organelles transported by kinesin in the fast transport component. The other pool, which contains the other developmentally regulated intermediate chains, is transported in slow component b. The mechanism of dynein regulation will therefore depend on which pool of dynein is recruited to function as the retrograde motor. In addition, the properties of the large pool of dynein associated with actin in slow component b are consistent with the hypothesis that this dynein may be the motor for microtubule transport in the axon.