Amyotrophic lateral sclerosis-associated mutant profilin 1 increases dendritic arborisation and spine formation in primary hippocampal neurons

Neurosci Lett. 2015 Nov 16:609:223-8. doi: 10.1016/j.neulet.2015.09.034. Epub 2015 Oct 21.

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and familial ALS accounts for 10% of cases. The identification of familial ALS mutations in the actin-binding protein profilin 1 directly implicates actin dynamics and regulation in the pathogenesis of ALS. The mechanism by which these mutations cause ALS is unknown. In this study we show that expression of the ALS-associated actin-binding deficient mutant of PFN1 (PFN1(C71G)) results in increased dendritic arborisation and spine formation, and cytoplasmic inclusions in cultured mouse hippocampal neurons.

Keywords: Actin cytoskeleton; Amyotrophic lateral sclerosis; Profilin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Animals
  • Dendrites / metabolism
  • Dendrites / ultrastructure*
  • Dendritic Spines / metabolism
  • Dendritic Spines / ultrastructure
  • HEK293 Cells
  • Hippocampus / cytology*
  • Humans
  • Mice, Inbred C57BL
  • Mutation
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Primary Cell Culture
  • Profilins / genetics
  • Profilins / metabolism*
  • Protein Aggregates

Substances

  • PFN1 protein, human
  • Profilins
  • Protein Aggregates