State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines.

Abstract:

:Dendritic spines are the postsynaptic sites of most excitatory synapses in the brain, and spine enlargement and shrinkage give rise to long-term potentiation and depression of synapses, respectively. Because spine structural plasticity is accompanied by remodeling of actin scaffolds, we hypothesized that the filamentous actin regulatory protein cofilin plays a crucial role in this process. Here we investigated the diffusional properties of cofilin, the actin-severing and depolymerizing actions of which are activated by dephosphorylation. Cofilin diffusion was measured using fluorescently labeled cofilin fusion proteins and two-photon imaging. We show that cofilins are highly diffusible along dendrites in the resting state. However, during spine enlargement, wild-type cofilin and a phosphomimetic cofilin mutant remain confined to the stimulated spine, whereas a nonphosphorylatable mutant does not. Moreover, inhibition of cofilin phosphorylation with a competitive peptide disables spine enlargement, suggesting that phosphorylated-cofilin accumulation is a key regulator of enlargement, which is localized to individual spines. Conversely, spine shrinkage spreads to neighboring spines, even though triggered by weaker stimuli than enlargement. Diffusion of exogenous cofilin injected into a pyramidal neuron soma causes spine shrinkage and reduced PSD95 in spines, suggesting that diffusion of dephosphorylated endogenous cofilin underlies the spreading of spine shrinkage and long-term depression.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Noguchi J,Hayama T,Watanabe S,Ucar H,Yagishita S,Takahashi N,Kasai H

doi

10.1038/srep32897

subject

Has Abstract

pub_date

2016-09-06 00:00:00

pages

32897

issn

2045-2322

pii

srep32897

journal_volume

6

pub_type

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