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Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity.

Publication ,  Journal Article
Hedrick, NG; Harward, SC; Hall, CE; Murakoshi, H; McNamara, JO; Yasuda, R
Published in: Nature
October 6, 2016

The Rho GTPase proteins Rac1, RhoA and Cdc42 have a central role in regulating the actin cytoskeleton in dendritic spines, thereby exerting control over the structural and functional plasticity of spines and, ultimately, learning and memory. Although previous work has shown that precise spatiotemporal coordination of these GTPases is crucial for some forms of cell morphogenesis, the nature of such coordination during structural spine plasticity is unclear. Here we describe a three-molecule model of structural long-term potentiation (sLTP) of murine dendritic spines, implicating the localized, coincident activation of Rac1, RhoA and Cdc42 as a causal signal of sLTP. This model posits that complete tripartite signal overlap in spines confers sLTP, but that partial overlap primes spines for structural plasticity. By monitoring the spatiotemporal activation patterns of these GTPases during sLTP, we find that such spatiotemporal signal complementation simultaneously explains three integral features of plasticity: the facilitation of plasticity by brain-derived neurotrophic factor (BDNF), the postsynaptic source of which activates Cdc42 and Rac1, but not RhoA; heterosynaptic facilitation of sLTP, which is conveyed by diffusive Rac1 and RhoA activity; and input specificity, which is afforded by spine-restricted Cdc42 activity. Thus, we present a form of biochemical computation in dendrites involving the controlled complementation of three molecules that simultaneously ensures signal specificity and primes the system for plasticity.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

October 6, 2016

Volume

538

Issue

7623

Start / End Page

104 / 108

Location

England

Related Subject Headings

  • rhoA GTP-Binding Protein
  • rho GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • cdc42 GTP-Binding Protein
  • Spatio-Temporal Analysis
  • Signal Transduction
  • Rats
  • Post-Synaptic Density
  • Neuropeptides
  • Neural Inhibition
 

Citation

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Hedrick, N. G., Harward, S. C., Hall, C. E., Murakoshi, H., McNamara, J. O., & Yasuda, R. (2016). Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity. Nature, 538(7623), 104–108. https://doi.org/10.1038/nature19784
Hedrick, Nathan G., Stephen C. Harward, Charles E. Hall, Hideji Murakoshi, James O. McNamara, and Ryohei Yasuda. “Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity.Nature 538, no. 7623 (October 6, 2016): 104–8. https://doi.org/10.1038/nature19784.
Hedrick NG, Harward SC, Hall CE, Murakoshi H, McNamara JO, Yasuda R. Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity. Nature. 2016 Oct 6;538(7623):104–8.
Hedrick, Nathan G., et al. “Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity.Nature, vol. 538, no. 7623, Oct. 2016, pp. 104–08. Pubmed, doi:10.1038/nature19784.
Hedrick NG, Harward SC, Hall CE, Murakoshi H, McNamara JO, Yasuda R. Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity. Nature. 2016 Oct 6;538(7623):104–108.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

October 6, 2016

Volume

538

Issue

7623

Start / End Page

104 / 108

Location

England

Related Subject Headings

  • rhoA GTP-Binding Protein
  • rho GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • cdc42 GTP-Binding Protein
  • Spatio-Temporal Analysis
  • Signal Transduction
  • Rats
  • Post-Synaptic Density
  • Neuropeptides
  • Neural Inhibition