title: Mtss1 promotes maturation and maintenance of cerebellar neurons via splice variant-specific effects.
abstract: Efficient coupling of the actin cytoskeleton to the cell membrane is crucial for histogenesis and maintenance of the nervous system. At this critical interface, BAR (Bin-Amphiphysin-Rvs) proteins regulate membrane bending, shown to be instrumental for mobility and morphogenesis of individual cells. Yet, the systemic significance of these proteins remains largely unexplored. Here, we probe the role of a prominent member of this protein family, the inverse-BAR protein Mtss1, for the development and function of a paradigmatic neuronal circuit, the cerebellar cortex. Mtss1-null mice show granule cell ectopias, dysmorphic Purkinje cells, malformed axons, and a protracted neurodegeneration entailing age-dependent motor deficits. In postmitotic granule cells, which transiently express Mtss1 while they migrate and form neurites, Mtss1 impinges on directional persistence and neuritogenesis. The latter effect can be specifically attributed to its exon 12a splice variant. Targeted re-expression of Mtss1 in Mtss1-null animals indicated that these pathologies were largely due to cell type-specific and intrinsic effects. Together, our results provide a mechanistic perspective on Mtss1 function for brain development and degeneration and relate it to structural features of this protein.
authors.affiliation: Anatomisches Institut, Anatomie and Zellbiologie, University of Bonn, Nussallee 10, 53115, Bonn, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Sistig
authors.affiliation: Anatomisches Institut, Anatomie and Zellbiologie, University of Bonn, Nussallee 10, 53115, Bonn, Germany.
authors.forename: Fanziska
authors.initials: F
authors.lastname: Lang
authors.affiliation: Anatomisches Institut, Anatomie and Zellbiologie, University of Bonn, Nussallee 10, 53115, Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wrobel
authors.affiliation: Anatomisches Institut, Anatomie and Zellbiologie, University of Bonn, Nussallee 10, 53115, Bonn, Germany.
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Baader
authors.affiliation: Anatomisches Institut, Anatomie and Zellbiologie, University of Bonn, Nussallee 10, 53115, Bonn, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Schilling
authors.affiliation: Anatomisches Institut, Anatomie and Zellbiologie, University of Bonn, Nussallee 10, 53115, Bonn, Germany. britta.eiberger@uni-bonn.de.
authors.forename: Britta
authors.initials: B
authors.lastname: Eiberger
mesh_terms: D000367:Age Factors; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration; D010641:Phenotype; D020033:Protein Isoforms; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D045442:Rotarod Performance Test
chemical_list: D008840:Microfilament Proteins; C473219:Mtss1 protein, mouse; D009363:Neoplasm Proteins; D020033:Protein Isoforms
keywords: Actin cytoskeleton; Cell migration; Neuritogenesis; Neurodegeneration