Distribution of Rho family GTPases in the adult rat hippocampus and cerebellum

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

doi:10.1016/s0169-328x(03)00121-9

Cited by 43 publications

(33 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These axons make essential connections to the highly complex dendritic system of the Purkinje cells, which forms a monolayer around the granular layer of the cerebellum and functions as the sole output from the cerebellar cortex. The neuronal localization of GEFT transcript correlates well with recent data showing that the Rho family of GTPases is highly expressed within the hippocampus as well as the molecular and granular layers in the cerebellum (43).…”

Section: Discussionsupporting

confidence: 85%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 85%

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

View full text Add to dashboard Cite

show abstract

“…However, RhoB, which has been relatively neglected in the neuroscience arena and is highly expressed in the brain (O'Kane et al, 2003a), can also activate ROCK (Leung et al, 1996). Additionally, RhoB can activate the actin regulatory protein mDia2 on endosomes (Wallar et al, 2007), and RhoB-containing endosomes harbor proteins involved in actin regulation (Sandilands et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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

McNair¹,

Spike²,

Guilding³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

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.

show abstract

“…In addition to being expressed in lymphocytes, RhoG is expressed in the central nervous system, in particular, in the hippocampus and cerebellum (22). This fact is of particular interest as mice deficient in Trio, an exchange factor for RhoG (3), display aberrant organization in several regions within the brain, including hippocampus formation (20).…”

Section: Discussionmentioning

confidence: 99%

Immunological Function in Mice Lacking the Rac-Related GTPase RhoG

Vigorito

Bell

Hebeis

et al. 2004

Molecular and Cellular Biology

View full text Add to dashboard Cite

RhoG is a low-molecular-weight GTPase highly expressed in lymphocytes that activates gene transcription and promotes cytoskeletal reorganization in vitro. To study the in vivo function of RhoG, we generated mice homozygous for a targeted disruption of the RhoG gene. Despite the absence of RhoG, the development of B and T lymphocytes was unaffected. However, there was an increase in the level of serum immunoglobulin G1 (IgG1) and IgG2b as well as a mild increase of the humoral immune response to thymus-dependent antigens. In addition, B-and T-cell proliferation in response to antigen receptor cross-linking was slightly increased. Although RhoG deficiency produces a mild phenotype, our experiments suggest that RhoG may contribute to the negative regulation of immune responses. The lack of a strong phenotype could indicate a functional redundancy of RhoG with other Rac proteins in lymphocytes.

show abstract

Distribution of Rho family GTPases in the adult rat hippocampus and cerebellum

Cited by 43 publications

References 40 publications

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

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

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

Immunological Function in Mice Lacking the Rac-Related GTPase RhoG

Contact Info

Product

Resources

About