The major brain isoform of Kif1b lacks the putative mitochondria-binding domain

Kinesin and kinesin superfamily proteins are molecular motors involved in i mportant intracellular functions such as organelle transport and cell divis ion. They are microtubule-activated ATPases composed of a motor domain that binds to microtubules and a cargo-binding domain that binds to specific or ganelles. While searching for the slow Wallerian degeneration mutation (Wld (s)) 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 K if1a. Kif1b is responsible for the movement of mitochondria along the axon, but the novel isoform containing the alternative C-terminal domain is like ly to have a different cargo-binding specificity, cDNA library screening an d Northern blot analysis indicate that the alternatively spliced form of Ki f1b containing the novel 3'end accounts for the most part of Kif1b expressi on. We also found more alternatively spliced exons that can give rise to he terogeneous transcripts. Therefore, alternative splicing, as well as multip le 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 tripli cation. There is, however, no evidence that Kif1b is the Wld gene.