Mtss1 promotes maturation and maintenance of cerebellar neurons via splice variant-specific effects

  • Thorsten Sistig
  • Fanziska Lang
  • Sebastian Wrobel
  • Stephan L. Baader
  • Karl Schilling
  • Britta Eiberger
Original Article
  • 146 Downloads

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.

Keywords

Actin cytoskeleton Cell migration Neuritogenesis Neurodegeneration 

Supplementary material

429_2017_1372_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 11 KB)
429_2017_1372_MOESM2_ESM.jpg (1.1 mb)
Supplementary material 2 (JPG 1122 KB)

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Thorsten Sistig
    • 1
  • Fanziska Lang
    • 1
  • Sebastian Wrobel
    • 1
  • Stephan L. Baader
    • 1
  • Karl Schilling
    • 1
  • Britta Eiberger
    • 1
  1. 1.Anatomisches Institut, Anatomie and ZellbiologieUniversity of BonnBonnGermany

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