摘要：SummarySpinal muscular atrophy (SMA) is a devastating motor neuron disorder caused by mutations in thesurvival motor neuron(SMN) gene. It remains unclear how SMN deficiency leads to the loss of motor neurons. By screeningSchizosaccharomyces pombe, we found that the growth defect of an SMN mutant can be alleviated by deletion of the actin-capping protein subunit geneacp1+. We show that SMN mutated cells have splicing defects in the profilin gene, which thus directly hinder actin cytoskeleton homeostasis including endocytosis and cytokinesis. We conclude that deletion ofacp1+in an SMN mutant background compensates for actin cytoskeleton alterations by restoring redistribution of actin monomers between different types of cellular actin networks. Our data reveal a direct correlation between an impaired function of SMN in snRNP assembly and defects in actin dynamics. They also point to important common features in the pathogenic mechanism of SMA and ALS.Graphical AbstractDisplay OmittedHighlights•Splicing defects in the profilin gene in anS. pombeSMN mutant•SMN mutant contains excessively polymerized actin•Altered actin dynamics in the SMN mutant hinders endocytosis and cytokinesis•Deletion of theacp1subunit restores actin dynamics in the SMN mutantBiological Sciences; Molecular Biology; Molecular Genetics; Cell Biology
