1. Splicing Defects of the Profilin Gene Alter Actin Dynamics in an S. pombe SMN Mutant
- Author
-
Kelly E. Nissen, Johann Soret, Nevan J. Krogan, Rémy Bordonné, Kristin L. Patrick, Marie Antoine, Yannick Gachet, Pauline Duc, Florence Rage, Ruben J. Cauchi, Rebecca Cacciottolo, Christine Guthrie, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie Intégrative (CBI), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Molecular biology ,animal diseases ,[SDV]Life Sciences [q-bio] ,Mutant ,02 engineering and technology ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,macromolecular substances ,Biology ,Neurodegenerative ,Article ,Molecular Genetics ,03 medical and health sciences ,Rare Diseases ,medicine ,Genetics ,snRNP ,Molecular genetics ,lcsh:Science ,Molecular Biology ,Actin ,ComputingMilieux_MISCELLANEOUS ,Pediatric ,Multidisciplinary ,Neurosciences ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Spinal muscular atrophy ,Cell Biology ,Biological Sciences ,021001 nanoscience & nanotechnology ,medicine.disease ,Actin cytoskeleton ,Life sciences ,3. Good health ,Cell biology ,nervous system diseases ,030104 developmental biology ,Profilin ,nervous system ,RNA splicing ,Spinal Muscular Atrophy ,Neurological ,biology.protein ,lcsh:Q ,0210 nano-technology ,Cytology ,Cytokinesis - Abstract
Summary Spinal muscular atrophy (SMA) is a devastating motor neuron disorder caused by mutations in the survival motor neuron (SMN) gene. It remains unclear how SMN deficiency leads to the loss of motor neurons. By screening Schizosaccharomyces pombe, we found that the growth defect of an SMN mutant can be alleviated by deletion of the actin-capping protein subunit gene acp1+. 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 of acp1+ 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 Abstract, Highlights • Splicing defects in the profilin gene in an S. pombe SMN mutant • SMN mutant contains excessively polymerized actin • Altered actin dynamics in the SMN mutant hinders endocytosis and cytokinesis • Deletion of the acp1 subunit restores actin dynamics in the SMN mutant, Biological Sciences; Molecular Biology; Molecular Genetics; Cell Biology
- Published
- 2020