Activity-Dependent Redistribution and Essential Role of Cortactin in Dendritic Spine Morphogenesis

Hering, Heike; Sheng, Morgan

doi:10.1523/jneurosci.23-37-11759.2003

Cited by 247 publications

(308 citation statements)

References 55 publications

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“…The volume of spines increased over 100% after Jasplakinolide treatment (Fig. 4b, d) (Hering and Sheng, 2003;Wang et al, 2007). Taken together, these results indicate that the fluorescence lifetime of the actin FRET sensor is a sensitive, selective and quantitative measure of actin polymerization.…”

Section: Actin Polymerization Quantified With the Megfp-sreach Pairmentioning

confidence: 54%

Highly sensitive and quantitative FRET–FLIM imaging in single dendritic spines using improved non-radiative YFP

2008

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Two-photon fluorescence lifetime imaging microscopy (TPFLIM) enables the quantitative measurements of fluorescence resonance energy transfer (FRET) in small subcellular compartments in light scattering tissue. We evaluated and optimized the FRET pair of mEGFP (monomeric EGFP with the A206K mutation) and REACh (non-radiative YFP variants) for TPFLIM. We characterized several mutants of REACh in terms of their "darkness," and their ability to act as a FRET acceptor for mEGFP in Hela cells and hippocampal neurons. Since the commonly used monomeric mutation A206K increases the brightness of REACh, we introduced a different monomeric mutation (F223R) which does not affect the brightness. Also, we found that the folding efficiency of original REACh, as measured by the fluorescence lifetime of a mEGFP-REACh tandem dimer, was low and variable from cell to cell. Introducing two folding mutations (F46L, Q69M) into REACh increased the folding efficiency by ∼50%, and reduced the variability of FRET signal. Pairing mEGFP with the new REACh (super-REACh, or sREACh) improved the signal-to-noise ratio compared to the mEGFPmRFP or mEGFP-original REACh pair by ∼50 %. Using this new pair, we demonstrated that the fraction of actin monomers in filamentous and globular forms in single dendritic spines can be quantitatively measured with high sensitivity. Thus, the mEGFP-sREACh pair is suited for quantitative FRET measurement by TPFLIM, and enables us to measure protein-protein interactions in individual dendritic spines in brain slices with high sensitivity.

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Section: Actin Polymerization Quantified With the Megfp-sreach Pairmentioning

confidence: 54%

Highly sensitive and quantitative FRET–FLIM imaging in single dendritic spines using improved non-radiative YFP

2008

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“…Cortactin expression supression 39 and CTTNBP2 knockdown in neurons 37 reduce the spine density 39 , indicating their importance for the formation and maintenance of the spines. Cortactin acts downstream of CTTNBP2 in spine morphogenesis, as the defects caused by CTTNBP2 knockdown can be rescued by cortactin overexpression but not by overexpressing a CTTNBP2 mutant protein that cannot bind cortactin 37 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Cortactin is an F-actin-binding protein and an activator of the Arp2/3 actin nucleation machinery [32,33]. Previous studies show that cortactin downregulation results in spine depletion, whereas its overexpression causes spine elongation [34]. It is also reported that overstimulation of NMDA receptors removes cortactin and thereby collapses dendritic spines, whereas stimulation with neurotrophic factors redistributes cortactin from dendritic shafts to spines to solidify synaptic transmission [35].…”

Section: Endophilin A1 Regulates Actin Cytoskeleton Reorganization Inmentioning

confidence: 99%

Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap

et al. 2015

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Dendritic spines are actin-rich membrane protrusions that are the major sites of excitatory synaptic input in the mammalian brain, and their morphological plasticity provides structural basis for learning and memory. Here we report that endophilin A1, with a well-established role in clathrin-mediated synaptic vesicle endocytosis at the presynaptic terminal, also localizes to dendritic spines and is required for spine morphogenesis, synapse formation and synaptic function. We identify p140Cap, a regulator of cytoskeleton reorganization, as a downstream effector of endophilin A1 and demonstrate that disruption of their interaction impairs spine formation and maturation. Moreover, we demonstrate that knockdown of endophilin A1 or p140Cap impairs spine stabilization and synaptic function. We further show that endophilin A1 regulates the distribution of p140Cap and its downstream effector, the F-actin-binding protein cortactin as well as F-actin enrichment in dendritic spines. Together, these results reveal a novel function of postsynaptic endophilin A1 in spine morphogenesis, stabilization and synaptic function through the regulation of p140Cap.

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Activity-Dependent Redistribution and Essential Role of Cortactin in Dendritic Spine Morphogenesis

Cited by 247 publications

References 55 publications

Highly sensitive and quantitative FRET–FLIM imaging in single dendritic spines using improved non-radiative YFP

Highly sensitive and quantitative FRET–FLIM imaging in single dendritic spines using improved non-radiative YFP

Dendritic spine actin cytoskeleton in autism spectrum disorder

Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap

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