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The Journal of Neuroscience, December 3, 2008, 28(49):13310-13319; doi:10.1523/JNEUROSCI.2727-08.2008

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Development/Plasticity/Repair
Formin Proteins of the DAAM Subfamily Play a Role during Axon Growth

Tamás Matusek,1 * Rita Gombos,1 * Anita Szécsényi,1 Natalia Sánchez-Soriano,2 Ágnes Czibula,1 Csilla Pataki,1 Anita Gedai,1 Andreas Prokop,2 István Raskó,1 and József Mihály1

1Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Hungary, and 2The Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom

Correspondence should be addressed to either of the following: József Mihály, Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62, Hungary, Email: mihaly{at}brc.hu; or Andreas Prokop, The Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK, Email: Andreas.Prokop{at}manchester.ac.uk

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.

Key words: axon growth; Formin; dDAAM; filopodia formation; Ena; Profilin; Rac


Received June 15, 2008; revised Oct. 20, 2008; accepted Oct. 24, 2008.

Correspondence should be addressed to either of the following: József Mihály, Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62, Hungary, Email: mihaly{at}brc.hu; or Andreas Prokop, The Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK, Email: Andreas.Prokop{at}manchester.ac.uk




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