title: The major brain isoform of kif1b lacks the putative mitochondria-binding domain.
abstract: Kinesin and kinesin superfamily proteins are molecular motors involved in important intracellular functions such as organelle transport and cell division. They are microtubule-activated ATPases composed of a motor domain that binds to microtubules and a cargo-binding domain that binds to specific organelles. While searching for the slow Wallerian degeneration mutation (WldS) on distal mouse Chromosome (Chr) 4, we have identified a member of the kinesin superfamily whose predicted gene product has the N-terminal motor domain of Kif1b and a novel C-terminal cargo-binding domain homologous to Kif1a. Kif1b is responsible for the movement of mitochondria along the axon, but the novel isoform containing the alternative C-terminal domain is likely to have a different cargo-binding specificity. cDNA library screening and Northern blot analysis indicate that the alternatively spliced form of Kif1b containing the novel 3'end accounts for the most part of Kif1b expression. We also found more alternatively spliced exons that can give rise to heterogeneous transcripts. Therefore, alternative splicing, as well as multiple genes, may contribute to the selective movement of diverse organelles by anterograde axonal transport. Kif1b maps on distal mouse Chr 4, within the Wld genetic candidate interval, but outside the recently identified triplication. There is, however, no evidence that Kif1b is the Wld gene.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
authors.forename: L
authors.initials: L
authors.lastname: Conforti
authors.forename: E A
authors.initials: EA
authors.lastname: Buckmaster
authors.forename: A
authors.initials: A
authors.lastname: Tarlton
authors.forename: M C
authors.initials: MC
authors.lastname: Brown
authors.forename: M F
authors.initials: MF
authors.lastname: Lyon
authors.forename: V H
authors.initials: VH
authors.lastname: Perry
authors.forename: M P
authors.initials: MP
authors.lastname: Coleman
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid
chemical_list: C490576:Kif1a protein, mouse; C490398:Kif1b protein, mouse; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D016547:Kinesins