Formin proteins of the DAAM subfamily play a role during axon growth.
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.
Matusek
Tamás
T
Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
Gombos
Rita
R
Szécsényi
Anita
A
Sánchez-Soriano
Natalia
N
Czibula
Agnes
A
Pataki
Csilla
C
Gedai
Anita
A
Prokop
Andreas
A
Raskó
István
I
Mihály
József
J
D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005260:Female; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D055495:Neurogenesis / Q000235:genetics*; D051304:Profilins / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C509803:DAAM protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C092744:ENA-VASP proteins; D051304:Profilins; D020744:rac GTP-Binding Proteins