Abstract:Rho family small GTPases are important regulators of neuronal development. Defective Rho regulation causes nervous system dysfunctions including mental retardation and Alzheimer’s disease. Rac1, a member of the Rho family, regulates dendritic spines and excitatory synapses, but relatively little is known about how synaptic Rac1 is negatively regulated. Breakpoint cluster region (BCR) is a Rac GTPase-activating protein known to form a fusion protein with the c-Abl tyrosine kinase in Philadelphia chromosome-posi… Show more
“…We found that BCR expression decreases through development (Fig. 5, B and C), which is supported by Oh et al (9), who observed decreased levels of BCR expression as mice age. It is tempting to speculate that this differential expression may be due to mutual regulation, although this remains to be investigated.…”
Section: The Ptb Domain Of Sh2d5 Interacts With a Specific Nxxf Motifsupporting
confidence: 89%
“…Because of the shared domain architecture of SH2D5 with Tyr(P) recognition adaptor proteins, we reasoned that a first step in unraveling the function of SH2D5 would be to analyze its interaction profiles in unstimulated cells and cells in which tyrosine phosphorylation is induced by exposure to pervanadate. Here, we characterize a novel interaction of the SH2D5 PTB domain with breakpoint cluster region protein (BCR), a regulator of Rho GTPases (9,10). We show enrichment of SH2D5 and BCR proteins in neuronal cell types.…”
Background: Src homology 2 domain containing protein 5 (SH2D5) is a previously uncharacterized protein that resembles the Shc proteins in structural organization. Results: SH2D5 binds to the breakpoint cluster region protein (BCR) in a phosphotyrosine-independent manner. Conclusion: SH2D5 controls neuronal morphology via BCR and Rac1. Significance: This is the first characterization of SH2D5 in neuronal signaling.
“…We found that BCR expression decreases through development (Fig. 5, B and C), which is supported by Oh et al (9), who observed decreased levels of BCR expression as mice age. It is tempting to speculate that this differential expression may be due to mutual regulation, although this remains to be investigated.…”
Section: The Ptb Domain Of Sh2d5 Interacts With a Specific Nxxf Motifsupporting
confidence: 89%
“…Because of the shared domain architecture of SH2D5 with Tyr(P) recognition adaptor proteins, we reasoned that a first step in unraveling the function of SH2D5 would be to analyze its interaction profiles in unstimulated cells and cells in which tyrosine phosphorylation is induced by exposure to pervanadate. Here, we characterize a novel interaction of the SH2D5 PTB domain with breakpoint cluster region protein (BCR), a regulator of Rho GTPases (9,10). We show enrichment of SH2D5 and BCR proteins in neuronal cell types.…”
Background: Src homology 2 domain containing protein 5 (SH2D5) is a previously uncharacterized protein that resembles the Shc proteins in structural organization. Results: SH2D5 binds to the breakpoint cluster region protein (BCR) in a phosphotyrosine-independent manner. Conclusion: SH2D5 controls neuronal morphology via BCR and Rac1. Significance: This is the first characterization of SH2D5 in neuronal signaling.
“…Some papers have reported that manipulations of the hippocampus impair novel object preference tasks (Mansuy et al, 1998;Pittenger et al, 2002;Oh et al, 2010). However, in a number of these studies such variation may be accounted for by differences in the experimental paradigms used, in particular the type or number of stimuli presented in the sample phase.…”
The role of the hippocampus in recognition memory is controversial. Recognition memory judgments may be made using different types of information, including object familiarity, an object's spatial location, or when an object was encountered. Experiment 1 examined the role of the hippocampus in recognition memory tasks that required the animals to use these different types of mnemonic information. Rats with bilateral cytotoxic lesions in the hippocampus or perirhinal or prefrontal cortex were tested on a battery of spontaneous object recognition tasks requiring the animals to make recognition memory judgments using familiarity (novel object preference); object-place information (object-in-place memory), or recency information (temporal order memory). Experiment 2 examined whether, when using different types of recognition memory information, the hippocampus interacts with either the perirhinal or prefrontal cortex. Thus, groups of rats were prepared with a unilateral cytotoxic lesion in the hippocampus combined with a lesion in either the contralateral perirhinal or prefrontal cortex. Rats were then tested in a series of object recognition memory tasks. Experiment 1 revealed that the hippocampus was crucial for object location, object-in-place, and recency recognition memory, but not for the novel object preference task. Experiment 2 revealed that object-in-place and recency recognition memory performance depended on a functional interaction between the hippocampus and either the perirhinal or medial prefrontal cortices. Thus, the hippocampus plays a role in recognition memory when such memory involves remembering that a particular stimulus occurred in a particular place or when the memory contains a temporal or object recency component.
“…RhoA, Rac and Cdc42 are the three best-studied Rho GTPases, which control the formation of distinct F-actin-based structures [39,40] . Studies have shown that RhoA and Rac1 are important for structural aspects of the mature neuron [41] and are related to learning and memory [42,43] . The present study set about to explore the relationship between the small Rho GTPases and drug withdrawal-induced hippocampal actin polymerization.…”
Aim: Actin rearrangements are induced in the dorsal hippocampus after conditioned morphine withdrawal, and involved in the formation of conditioned place aversion. In the present study, we investigated the mechanisms underlying the actin rearrangements in rat dorsal hippocampus induced by conditioned morphine withdrawal. Methods: The RhoA-ROCK pathway inhibitor Y27632 (8.56 μg/1 μL per side) or the Rac1 inhibitor NSC23766 (25 μg/1 μL per side) was microinjected into the dorsal hippocampus of rats. Conditioned place aversion (CPA) induced by naloxone-precipitated morphine withdrawal was assessed. Crude synaptosomal fraction of hippocampus was prepared, and the amount of F-actin and G-actin was measured with an Actin Polymerization Assay Kit. Results: Conditioned morphine withdrawal significantly increased actin polymerization in the dorsal hippocampus at 1 h following the naloxone injection. Preconditioning with microinjection of Y27632, but not NSC23766, attenuated CPA, and blocked the increase in actin polymerization in the dorsal hippocampus. Conclusion: Our results suggest that the small GTPase RhoA, but not Rac1, in the dorsal hippocampus is responsible for CPA formation, mainly through its regulation of actin rearrangements.
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