RAFT-LIKE TRANSPORT OF CYTOSKELETAL ELEMENTS IN MAMMALS

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The distinct morphology of neurons requires active transport mechanisms for the appropriate and timely delivery of newly synthesized proteins, yet active transport places the burden on neurons of having to develop and maintain cytoskeletal tracks for directed locomotion. Evidence from Chlamydomonas reinhardtii indicates that kinesin II associates with large, raft-like structures during intraflagellar transport (IFT). The recent cloning of NGD5, a homologue of a member of Chlamydomonas IFT rafts, raises the possibility that an analogous system is utilized in mammals. To test if NGD5 and kinesin II are members of an analogous system in mammals utilized for transporting cytoskeletal components is proposed. Colocalization and coimmunoprecipitation will target specific neuronal population for further, more detailed analysis. Ultimately, analysis of transport and structure in neurons with targeted gene disruptions of NGD5 and kinesin II will be utilized to directly test the hypothesis. Evidence indicates that the misaccumulation of neurofilaments can lead to amyotrophic lateral sclerosis (ALS)-like pathology. Additionally, slowing of axonal transport is an early event associated with the toxicity of ALS-linked SOD 1 mutations. Therefore, an understanding of the mechanisms involved in protein transport is fundamental to our understanding of the nervous system and may provide insight into the pathogenesis of neurodegenerative diseases.