Structure And Function Of Cytoplasmic Motors

Neurological Disorders And Stroke

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Abstract

TRANSPORT PROJECT[unreadable] [unreadable] The squid giant axon is an important model for understanding axonal transport. Conventional kinesin, the founding member of a diverse and functionally important group of molecular motor proteins, was discovered in squid and its role there attributed to the transport of vesicles in axons. Recently we have completed an EST (Expressed Sequence Tag) project aimed at identifying other motors in the squid nervous system. We found 83 overlapping sequences that encode five cellular myosins (non-muscle), three dynein heavy chains, and six new kinesins. One of the new kinesins (K-165) fractionates with axoplasmic organelles, and is found only at organelle interfaces with microtubules in the axon. This kinesin, a Kinesin-3, appears to be the motor actually responsible for axonal transport, though Kinesin-1 may make a contribution as well. In addition to new motors, the EST project has identified genes implicated in neurological disease. This includes Amyloid Precursor Protein (APP), a transmembrane protein with a role in Alzheimer's Disease (AD), and two genes involved in Niemann Pick Disease. This EST resource has been shared with seventeen laboratories working on squid to study basic and biomedical research. We also used a new technique we developed to label a subpopulation of the fibers in the actin cytoskeleton with photoactivatable-EGFP-actin. This technique allowed lateral motions of actin accompanied by synchronous lateral movement and clustering of beta 1 integrins to be observed. These results suggest that actin positioning activates integrins to provide a mechanism for cells to seek new adhesion sites and preferred directions of migration.