Dendritic spine geometry can localize GTPase signaling in neurons

Molecular Biology of the Cell
Samuel A RamirezDaniel J Lew

Abstract

Dendritic spines are the postsynaptic terminals of most excitatory synapses in the mammalian brain. Learning and memory are associated with long-lasting structural remodeling of dendritic spines through an actin-mediated process regulated by the Rho-family GTPases RhoA, Rac, and Cdc42. These GTPases undergo sustained activation after synaptic stimulation, but whereas Rho activity can spread from the stimulated spine, Cdc42 activity remains localized to the stimulated spine. Because Cdc42 itself diffuses rapidly in and out of the spine, the basis for the retention of Cdc42 activity in the stimulated spine long after synaptic stimulation has ceased is unclear. Here we model the spread of Cdc42 activation at dendritic spines by means of reaction-diffusion equations solved on spine-like geometries. Excitable behavior arising from positive feedback in Cdc42 activation leads to spreading waves of Cdc42 activity. However, because of the very narrow neck of the dendritic spine, wave propagation is halted through a phenomenon we term geometrical wave-pinning. We show that this can account for the localization of Cdc42 activity in the stimulated spine, and, of interest, retention is enhanced by high diffusivity of Cdc42. Our findings are...Continue Reading

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Citations

Aug 14, 2019·Scientific Reports·Andrea CugnoPadmini Rangamani
Mar 16, 2021·The Journal of General Physiology·Kazuki ObashiShigeo Okabe
Apr 27, 2021·ELife·Jian-Geng ChiouDaniel J Lew
Jun 9, 2021·Communications Biology·Natasha S Savage
Jul 16, 2021·PLoS Computational Biology·Samuel A RamirezTimothy C Elston
Jul 15, 2021·PLoS Computational Biology·Debojyoti BiswasPablo A Iglesias

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Methods Mentioned

BETA
GTPases
GTPase
nucleotide exchange

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