Activation of Rho GTPases by synaptic transmission in the hippocampus

O’Kane, E.M.; Stone, T.W.; Morris, Brian J.

doi:10.1046/j.1471-4159.2003.02102.x

Cited by 46 publications

(34 citation statements)

References 27 publications

(27 reference statements)

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“…؊/؊ mice have reduced short-term plasticity We previously demonstrated that LTP induction by HFS is associated with specific activation of RhoB via NMDA receptor stimulation (O'Kane et al, 2003b). Here, we show that while basal levels of synaptic transmission are normal, short-term plasticity was impaired in RhoB Ϫ/Ϫ mouse hippocampus.…”

Section: Rhobmentioning

confidence: 48%

“…RhoA, Rac1, and CDC42 have all been implicated in the development and maintenance of dendritic structures, including spines (Luo et al, 1996;Nakayama et al, 2000;Tashiro et al, 2000). However, as evidence suggests that induction of LTP activates RhoB but not RhoA or Rac1 (O'Kane et al, 2003b), the hypothesis that RhoB mediates altered spine morphology during plasticity is attractive.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated that LTP is associated with specific RhoB activation (O'Kane et al, 2003b). To assess the contribution of RhoB to synaptic plasticity mechanisms, we investigated the electrophysiological and morphological consequences of RhoB gene deletion and found that reduced synaptic plasticity accompanies reduced cofilin phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

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A Role for RhoB in Synaptic Plasticity and the Regulation of Neuronal Morphology

McNair¹,

Spike²,

Guilding³

et al. 2010

J. Neurosci.

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Actin-rich dendritic spines are the locus of excitatory synaptic transmission and plastic events such as long-term potentiation (LTP).Morphological plasticity of spines accompanies activity-dependent changes in synaptic strength. Several Rho GTPase family members are implicated in regulating neuronal and, in particular, spine structure via actin and the actin-binding protein cofilin. However, despite expression in hippocampus and cortex, its ability to modulate actin-regulatory proteins, and its induction during aging, RhoB has been relatively neglected. We previously demonstrated that LTP is associated with specific RhoB activation. Here, we further examined its role in synaptic function using mice with genetic deletion of the RhoB GTPase (RhoB Ϫ/Ϫ mice). Normal basal synaptic transmission accompanied reduced paired-pulse facilitation and post-tetanic potentiation in the hippocampus of RhoB Ϫ/Ϫ mice. Early phase LTP was significantly reduced in RhoB Ϫ/Ϫ animals, whereas the later phase was unaffected. In wild-type mice (RhoB ϩ/ϩ ), Western blot analysis of potentiated hippocampus showed significant increases in phosphorylated cofilin relative to nonpotentiated slices, which were dramatically impaired in RhoB Ϫ/Ϫ slices. There was also a deficit in phosphorylated Lim kinase levels in the hippocampus from RhoB Ϫ/Ϫ mice. Morphological analysis suggested that lack of RhoB resulted in increased dendritic branching and decreased spine number. Furthermore, an increase in the proportion of stubby relative to thin spines was observed. Moreover, spines demonstrated increased length along with increased head and neck widths. These data implicate RhoB in cofilin regulation and dendritic and spine morphology, highlighting its importance in synaptic plasticity at a structural and functional level.

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Section: Rhobmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Role for RhoB in Synaptic Plasticity and the Regulation of Neuronal Morphology

McNair¹,

Spike²,

Guilding³

et al. 2010

J. Neurosci.

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“…Kalirin, a GEF homologous to GEFT in the Dbl homology and pleckstrin homology domains, has been shown to regulate dendritic spine formation in hippocampal neurons in response to ephrin stimulation (41). In addition, it has been demonstrated that the Rho family of small GTPases is activated by synaptic transmission during both low frequency stimulation and long term potentiation in the hippocampus (42). Within the cerebellum, granule cells function by sending excitatory bifurcate axons along the cerebellar cortex in the parallel fiber pathway.…”

Section: Discussionmentioning

confidence: 99%

GEFT, A Rho Family Guanine Nucleotide Exchange Factor, Regulates Neurite Outgrowth and Dendritic Spine Formation

Bryan

Kumar

Stafford

et al. 2004

Journal of Biological Chemistry

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The Rho family of small GTPases controls a wide range of cellular processes in eukaryotic cells, such as normal cell growth, proliferation, differentiation, gene regulation, actin cytoskeletal organization, cell fate determination, and neurite outgrowth. The activation of RhoGTPases requires the exchange of GDP for GTP, a process catalyzed by the Dbl family of guanine nucleotide exchange factors. We demonstrate that a newly identified guanine nucleotide exchange factor, GEFT, is widely expressed in the brain and highly concentrated in the hippocampus, and the Purkinje and granular cells of the cerebellum. Exogenous expression of GEFT promotes dendrite outgrowth in hippocampal neurons, resulting in spines with larger size as compared with control spines. In neuroblastoma cells, GEFT promotes the active GTPbound state of Rac1, Cdc42, and RhoA and increases neurite outgrowth primarily via Rac1. Furthermore, we demonstrated that PAK1 and PAK5, both downstream effectors of Rac1/Cdc42, are necessary for GEFT-induced neurite outgrowth. AP-1 and NF-B, two transcriptional factors involved in neurite outgrowth and survival, were up-regulated in GEFT-expressing cells. Together, our data suggest that GEFT enhances dendritic spine formation and neurite outgrowth in primary neurons and neuroblastoma cells, respectively, through the activation of Rac/Cdc42-PAK signaling pathways.

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“…Rho GTPase activation (34), increase in spine F-actin content (6), and morphologic changes of spines (4,5), are associated with LTP. In addition, the pharmacological manipulation of Rho GTPases affects LTP (35).…”

Section: Enhancement Of Hippocampal Neurotransmission In Cnf1-treatedmentioning

confidence: 99%

Enhancement of learning and memory after activation of cerebral Rho GTPases

Diana

Valentini

Travaglione

et al. 2007

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

118

115

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The mechanism whereby the morphology and connectivity of the dendritic tree is regulated depends on an actin dynamics that, in turn, is controlled by Rho GTPases, a family of small GTP-binding proteins encompassing Rho, Rac, and Cdc42 subfamilies. Cytotoxic necrotizing factor 1 (CNF1), a protein toxin from Escherichia coli, constitutively activates Rho GTPases, thus leading to remodeling of the actin cytoskeleton in intact cells. Here, we show that the modulation of cerebral RhoA and Rac1 activity induced by CNF1 in mice leads to (i) rearrangement of cerebral actin cytoskeleton, (ii) enhanced neurotransmission and synaptic plasticity, and (iii) improved learning and memory in various behavioral tasks. The effects persist for weeks and are not observed in mice treated with a recombinant CNF1, in which the enzymatic activity was abolished by substituting serine to cysteine at position 866. The results suggest that learning ability can be improved through pharmacological manipulation of neural connectivity.cytotoxic necrotizing factor 1 ͉ brain ͉ bacterial toxins ͉ dendritic spines ͉ drug therapy

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Activation of Rho GTPases by synaptic transmission in the hippocampus

Cited by 46 publications

References 27 publications

A Role for RhoB in Synaptic Plasticity and the Regulation of Neuronal Morphology

A Role for RhoB in Synaptic Plasticity and the Regulation of Neuronal Morphology

GEFT, A Rho Family Guanine Nucleotide Exchange Factor, Regulates Neurite Outgrowth and Dendritic Spine Formation

Enhancement of learning and memory after activation of cerebral Rho GTPases

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