[
International Worm Meeting,
2005]
Mutations in human spastin (SPG4) cause an autosomal dominant form of hereditary spastic paraplegia, which is characterized by weakness, spasticity and loss of the vibratory sense in the lower limbs. Sequence analysis revealed that spastin is composed of the AAA (ATPases associated with diverse cellular activities) domain in the C-terminal region and the MIT (microtubule interacting and trafficking) domain in the N-terminal region, suggesting an active role in cytoskeleton interactions. Recently, it was reported that spastin interacts dynamically with microtubules and displays microtubule-severing activity by in vivo and in vitro experiments.A plausible C. elegans homologue of spastin (C24B5.2) has been identified by homology search and phylogenetic analyses. To understand the function of the spastin homologue, we characterized the deletion mutant of C24B5.2, which has a 917 bp deletion in the C24B5.2 gene (obtained from Dr. S. Mitani, National Bioresource Project). The mutant worms showed a slightly slow growth, the reduction of brood size, and the abnormal gonad and multi vulva phenotypes, while they did not show any defects on motility, defecation and life spans. In situ hybridization analysis revealed that the gene is expressed in the whole bodies of young adult worms, particularly intestine, gonad and vulva. These results suggest that C24B5.2 may play an important role in the gonadal development. Cell fractionation and immunofluorescence analyses revealed that C24B5.2 is localized at perinuclear and cytoplasmic regions in embryos. We also found that C24B5.2 has two isoforms generated by alternative splicing depending on the developmental stages: the longer form appears in embryonic stage, while the shorter form in all the developmental stages. We will discuss possible roles of the spastin homologue in C. elegans.