Formin proteins of the DAAM subfamily play a role during axon growth

J Neurosci. 2008 Dec 3;28(49):13310-9. doi: 10.1523/JNEUROSCI.2727-08.2008.

Abstract

The regulation of growth cone actin dynamics is a critical aspect of axonal growth control. Among the proteins that are directly involved in the regulation of actin dynamics, actin nucleation factors play a pivotal role by promoting the formation of novel actin filaments. However, the essential nucleation factors in developing neurons have so far not been clearly identified. Here, we show expression data, and use true loss-of-function analysis and targeted expression of activated constructs to demonstrate that the Drosophila formin DAAM plays a critical role in axonal morphogenesis. In agreement with this finding, we show that dDAAM is required for filopodia formation at axonal growth cones. Our genetic interaction, immunoprecipitation and protein localization studies argue that dDAAM acts in concert with Rac GTPases, Profilin and Enabled during axonal growth regulation. We also show that mouse Daam1 rescues the CNS defects observed in dDAAM mutant flies to a high degree, and vice versa, that Drosophila DAAM induces the formation of neurite-like protrusions when expressed in mouse P19 cells, strongly suggesting that the function of DAAM in developing neurons has been conserved during evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line
  • Central Nervous System / cytology
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism
  • Conserved Sequence / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Evolution, Molecular
  • Female
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Male
  • Mice
  • Mutation / genetics
  • Neural Pathways / cytology
  • Neural Pathways / embryology
  • Neural Pathways / metabolism
  • Neurites / metabolism
  • Neurites / ultrastructure
  • Neurogenesis / genetics*
  • Profilins / metabolism
  • rac GTP-Binding Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DAAM protein, Drosophila
  • DNA-Binding Proteins
  • Drosophila Proteins
  • ENA-VASP proteins
  • Profilins
  • rac GTP-Binding Proteins