Regulation of dendritic spine morphology by an NMDA receptor‐associated Rho GTPase‐activating protein, p250GAP

Nakazawa, Takahiro; Kuriu, Toshihiko; Tezuka, T.; Umemori, Hisashi; Okabe, Susumu; Yamamoto, Tadashi

doi:10.1111/j.1471-4159.2008.05335.x

Cited by 59 publications

(56 citation statements)

References 50 publications

(172 reference statements)

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“…In contrast, a gain-of-function experiment in hippocampal neurons overexpressing ARHGAP32 led to a decrease in the spine width but an increase in the neck length 283 . ARHGAP32 interacts with the NR2B subunit of the NMDA receptor and promotes the activation of the RhoGTPase RhoA in response to NMDA activation 283 ( Figure 6).…”

Section: Arhgap32 (Arhgap32)mentioning

confidence: 77%

“…Arhgap32 gene silencing in cultured hippocampal neurons has been shown to produce an increased dendritic spine head width without affecting the length of the spines or their density along the dendritic shaft 283 . In contrast, a gain-of-function experiment in hippocampal neurons overexpressing ARHGAP32 led to a decrease in the spine width but an increase in the neck length 283 .…”

Section: Arhgap32 (Arhgap32)mentioning

confidence: 99%

See 1 more Smart Citation

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Section: Arhgap32 (Arhgap32)mentioning

confidence: 77%

Section: Arhgap32 (Arhgap32)mentioning

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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“…Several guanine nucleotide exchange factors and GTPaseactivating proteins (GAPs), including p250GAP, Lfc, and ␤PIX, which are expressed in the mammalian neocortex, regulate dendritic morphology in response to neural activity (Ryan et al, 2005;Nakazawa et al, 2008;Saneyoshi et al, 2008). Similar mechanisms might work in axons, although additional investigation is necessary because the role of Rho GTPases in activitydependent axonal branching has not been realized until the present study.…”

Section: Discussionmentioning

confidence: 95%

“…It has been shown that Rho GTPases are involved in activitydependent spine formation and dendritic arborization (Li et al, 2000;Sin et al, 2002;Schubert et al, 2006;Nakazawa et al, 2008). Several guanine nucleotide exchange factors and GTPaseactivating proteins (GAPs), including p250GAP, Lfc, and ␤PIX, which are expressed in the mammalian neocortex, regulate dendritic morphology in response to neural activity (Ryan et al, 2005;Nakazawa et al, 2008;Saneyoshi et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Role of RhoA in Activity-Dependent Cortical Axon Branching

Ohnami¹,

Endo²,

Hirai³

et al. 2008

J. Neurosci.

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During development, axon branching is influenced by sensory-evoked and spontaneous neural activity. We studied the molecular mechanism that underlies activity-dependent branch formation at horizontally elongating axons (horizontal axons) in the upper cortical layers, focusing on Rho family small GTPases. Axonal labeling with enhanced yellow fluorescent protein showed that horizontal axons formed several branches in organotypic slice cultures. This branch formation was considerably increased by introducing constitutively active RhoA and was slightly inhibited by dominant-negative RhoA. Activators and inhibitors of endogenous RhoA signaling also promoted and inhibited branching, respectively. Daily imaging of horizontal axon growth further demonstrated that constitutively active RhoA increased the dynamic addition and loss of branches. Moreover, the amount of active RhoA relative to the total amount of RhoA was examined by a pull-down assay in cortical slices treated with sodium channel or glutamate receptor blockers to reduce neural activity. Activity blockade significantly decreased active RhoA compared with normal culture conditions, in which spontaneous firing is prominent. These findings suggest that RhoA signaling acts as a positive regulator for activity-dependent axon branching in cortical neurons.

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“…It has also been shown that activity blockade inhibits axon responsiveness to ephrin-As and leads to the disruption of topographic mapping in the retinotectal projection (44). Finally, regulation of cytoplasmic signaling such as that driven by NMDA receptor activation may also be specifically involved in activity-dependent processes (45,46). In summary, TC axon branching was promoted only when both thalamic and cortical cells were coactivated in vitro.…”

Section: Discussionmentioning

confidence: 96%

Role of pre- and postsynaptic activity in thalamocortical axon branching

Yamada

Uesaka

Hayano

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Axonal branching is thought to be regulated not only by genetically defined programs but also by neural activity in the developing nervous system. Here we investigated the role of pre-and postsynaptic activity in axon branching in the thalamocortical (TC) projection using organotypic coculture preparations of the thalamus and cortex. Individual TC axons were labeled with enhanced yellow fluorescent protein by transfection into thalamic neurons. To manipulate firing activity, a vector encoding an inward rectifying potassium channel (Kir2.1) was introduced into either thalamic or cortical cells. Firing activity was monitored with multielectrode dishes during culturing. We found that axon branching was markedly suppressed in Kir2.1-overexpressing thalamic cells, in which neural activity was silenced. Similar suppression of TC axon branching was also found when cortical cell activity was reduced by expressing Kir2.1. These results indicate that both preand postsynaptic activity is required for TC axon branching during development.D uring development, axons navigate to their target regions and form elaborate branches when they make synaptic connections with multiple target cells. It has been demonstrated that axon guidance to the target region is regulated by attractive and repulsive molecular cues that are expressed in particular spatiotemporal patterns (1). Similar molecular mechanisms are thought to influence axon branching (2). In addition, neural activity such as firing and synaptic activity can also affect branch formation (3-5). An intriguing and unanswered problem is how neural activity regulates axonal branching.The thalamocortical (TC) projection in the mammalian cortex is a well-characterized system in which to investigate activity-dependent axon branching. In the developing sensory cortices, TC axons form elaborate terminal arbors, whose size and complexity are altered by neural activity. In the primary visual cortex of higher mammals such as cats, ferrets, and monkeys, TC axons serving left and right eyes are segregated into eye-specific stripes (6). This segregation is established during development (7), but is disrupted by blockade of retinal activity (8, 9). Regarding individual axon arbors, it is known that after monocular deprivation, TC axons serving the deprived and nondeprived eyes shrink and expand their arbors, respectively (10, 11). A recent study in which monocular deprivation was combined with silencing cortical activity has further suggested that correlations between pre-and postsynaptic activity play a dominant role in segregation of axon arbors (12). In accordance with this view, molecular machinery in pre-and postsynaptic sites has also been shown to affect arbor formation of TC axons in the somatosensory cortex (13-15). However, the relative role of pre-and postsynaptic activity in TC axon branching remains unclear.To address this issue, we investigated TC axon branching in cocultures of the thalamus and cortex by manipulating the firing activity of thalamic (presynaptic) and cortical (...

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Regulation of dendritic spine morphology by an NMDA receptor‐associated Rho GTPase‐activating protein, p250GAP

Cited by 59 publications

References 50 publications

Dendritic spine actin cytoskeleton in autism spectrum disorder

Dendritic spine actin cytoskeleton in autism spectrum disorder

Role of RhoA in Activity-Dependent Cortical Axon Branching

Role of pre- and postsynaptic activity in thalamocortical axon branching

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