Cdc42 participates in the regulation of ADF/cofilin and retinal growth cone filopodia by brain derived neurotrophic factor - PubMed (original) (raw)

. 2006 Feb 5;66(2):103-14.

doi: 10.1002/neu.20204.

Affiliations

• PMID: 16215999
• DOI: 10.1002/neu.20204

Cdc42 participates in the regulation of ADF/cofilin and retinal growth cone filopodia by brain derived neurotrophic factor

Tsan-Ju Chen et al. J Neurobiol. 2006.

Abstract

Rho family GTPases have important roles in mediating the effects of guidance cues and growth factors on the motility of neuronal growth cones. We previously showed that the neurotrophin BDNF regulates filopodial dynamics on growth cones of retinal ganglion cell axons through activation of the actin regulatory proteins ADF and cofilin by inhibiting a RhoA-dependent pathway that phosphorylates (inactivates) ADF/cofilin. The GTPase Cdc42 has also been implicated in mediating the effects of positive guidance cues. In this article we investigated whether Cdc42 is involved in the effects of BDNF on filopodial dynamics. BDNF treatment increases Cdc42 activity in retinal neurons, and neuronal incorporation of constitutively active Cdc42 mimics the increases in filopodial number and length. Furthermore, constitutively active and dominant negative Cdc42 decreased and increased, respectively, the activity of RhoA in retinal growth cones, indicating crosstalk between these GTPases in retinal growth cones. Constitutively active Cdc42 mimicked the activation of ADF/cofilin that resulted from BDNF treatment, while dominant negative Cdc42 blocked the effects of BDNF on filopodia and ADF/cofilin. The inability of dominant negative Cdc42 to block ADF/cofilin activation and stimulation of filopodial dynamics by the ROCK inhibitor Y-27632 indicate interaction between Cdc42 and RhoA occurs upstream of ROCK. Our results demonstrate crosstalk occurs between GTPases in mediating the effects of BDNF on growth cone motility, and Cdc42 activity can promote actin dynamics via activation of ADF/cofilin.

PubMed Disclaimer

Similar articles

• Regulating actin dynamics in neuronal growth cones by ADF/cofilin and rho family GTPases.
  Kuhn TB, Meberg PJ, Brown MD, Bernstein BW, Minamide LS, Jensen JR, Okada K, Soda EA, Bamburg JR. Kuhn TB, et al. J Neurobiol. 2000 Aug;44(2):126-44. J Neurobiol. 2000. PMID: 10934317 Review.
• Brain-derived neurotrophic factor regulation of retinal growth cone filopodial dynamics is mediated through actin depolymerizing factor/cofilin.
  Gehler S, Shaw AE, Sarmiere PD, Bamburg JR, Letourneau PC. Gehler S, et al. J Neurosci. 2004 Nov 24;24(47):10741-9. doi: 10.1523/JNEUROSCI.2836-04.2004. J Neurosci. 2004. PMID: 15564592 Free PMC article.
• FRET imaging in nerve growth cones reveals a high level of RhoA activity within the peripheral domain.
  Nakamura T, Aoki K, Matsuda M. Nakamura T, et al. Brain Res Mol Brain Res. 2005 Oct 3;139(2):277-87. doi: 10.1016/j.molbrainres.2005.05.030. Brain Res Mol Brain Res. 2005. PMID: 16024133
• Signalling and crosstalk of Rho GTPases in mediating axon guidance.
  Yuan XB, Jin M, Xu X, Song YQ, Wu CP, Poo MM, Duan S. Yuan XB, et al. Nat Cell Biol. 2003 Jan;5(1):38-45. doi: 10.1038/ncb895. Nat Cell Biol. 2003. PMID: 12510192
• Regulating filopodial dynamics through actin-depolymerizing factor/cofilin.
  Fass J, Gehler S, Sarmiere P, Letourneau P, Bamburg JR. Fass J, et al. Anat Sci Int. 2004 Dec;79(4):173-83. doi: 10.1111/j.1447-073x.2004.00087.x. Anat Sci Int. 2004. PMID: 15633455 Review.

Cited by

• Activity-dependent rapid local RhoA synthesis is required for hippocampal synaptic plasticity.
  Briz V, Zhu G, Wang Y, Liu Y, Avetisyan M, Bi X, Baudry M. Briz V, et al. J Neurosci. 2015 Feb 4;35(5):2269-82. doi: 10.1523/JNEUROSCI.2302-14.2015. J Neurosci. 2015. PMID: 25653381 Free PMC article.
• The growth cone cytoskeleton in axon outgrowth and guidance.
  Dent EW, Gupton SL, Gertler FB. Dent EW, et al. Cold Spring Harb Perspect Biol. 2011 Mar 1;3(3):a001800. doi: 10.1101/cshperspect.a001800. Cold Spring Harb Perspect Biol. 2011. PMID: 21106647 Free PMC article. Review.
• Automated analysis of filopodial length and spatially resolved protein concentration via adaptive shape tracking.
  Saha T, Rathmann I, Viplav A, Panzade S, Begemann I, Rasch C, Klingauf J, Matis M, Galic M. Saha T, et al. Mol Biol Cell. 2016 Nov 7;27(22):3616-3626. doi: 10.1091/mbc.E16-06-0406. Epub 2016 Aug 17. Mol Biol Cell. 2016. PMID: 27535428 Free PMC article.
• Altered expression of CDC42 signaling pathway components in cortical layer 3 pyramidal cells in schizophrenia.
  Datta D, Arion D, Corradi JP, Lewis DA. Datta D, et al. Biol Psychiatry. 2015 Dec 1;78(11):775-85. doi: 10.1016/j.biopsych.2015.03.030. Epub 2015 Apr 11. Biol Psychiatry. 2015. PMID: 25981171 Free PMC article.
• Cofilin 1 activation prevents the defects in axon elongation and guidance induced by extracellular alpha-synuclein.
  Tilve S, Difato F, Chieregatti E. Tilve S, et al. Sci Rep. 2015 Nov 12;5:16524. doi: 10.1038/srep16524. Sci Rep. 2015. PMID: 26558842 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Wiley

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal