Roles of Disrupted-In-Schizophrenia 1-Interacting Protein Girdin in Postnatal Development of the Dentate Gyrus

Enomoto, Atsushi; Asai, Naoya; Namba, Tsuneo; Wang, Yun; Kato, Takuya; Tanaka, Motoki; Tatsumi, Hitoshi; Taya, Shinichiro; Tsuboi, Daisuke; Kuroda, Kensuke; Kaneko, Naoko; Sawamoto, Kazunobu; Miyamoto, Reiko; Jijiwa, Mayumi; Murakumo, Yoshiki; Sokabe, Masahiro; Seki, Tatsunori; Kaibuchi, Kozo; Takahashi, Masahide

doi:10.1016/j.neuron.2009.08.015

Cited by 168 publications

(203 citation statements)

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“…Akt has a wide range of substrates; the activation of Akt and its substrates regulates many important cellular functions, such as cell survival, growth, proliferation, metabolism, migration and invasion (Zhang et al, 2009). The novel Akt substrate, Girdin, binds to the actin cytoskeleton (Enomoto et al, 2005) and both the expression and phosphorylation of Girdin are important in the progression of some types of cancer (Jiang et al, 2008), postnatal angiogenesis of immature endothelial cells (Kitamura et al, 2008) and neurogenesis of neural progenitor cells (Enomoto et al, 2009). These findings suggest that Girdin may be involved in the function of We found the highest frequency of Girdin positivity and phosphorylation in grade IV tumors (GBM) (Figures 1b and c).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, Akt-mediated invasion is one of the prominent characteristics of BTSCs. Girdin functions in actin remodeling at the leading edge of migrating cells (Enomoto et al, 2005), and migration and positioning of neural stem cells in the dentate gyrus of the hippocampus during the early postnatal period (Enomoto et al, 2009). Therefore, we aimed to investigate the possible influence of Girdin depletion on the migratory capability of GBM cells.…”

Section: Girdin Depletion Induces Differentiation From Gbm Stem Cellsmentioning

confidence: 99%

“…In cultured fibroblasts and endothelial cells, Girdin functions in the remodeling of actin filaments in the lamellipodia at the leading edges of migrating cells (Enomoto et al, 2005) and sprouting of new blood vessels during development of the postnatal brain cortex (Kitamura et al, 2008). Recently, Girdin was found to have a role in neurogenesis in the dentate gyrus, both postnatally and constitutively throughout adult life (Enomoto et al, 2009;Kim et al, 2009). Girdin is highly expressed in immature progenitor cells that differentiate from neural stem cells in the subgranular zone of the dentate gyrus, and regulates the migration and positioning of newborn dentate granule cells.…”

Section: Introductionmentioning

confidence: 99%

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Girdin maintains the stemness of glioblastoma stem cells

et al. 2011

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Glioblastomas (GBMs) are the most common and aggressive type of brain tumor. GBMs usually show hyperactivation of the PI3K-Akt pathway, a pro-tumorigenic signaling cascade that contributes to pathogenesis. Girdin, an actin-binding protein identified as a novel substrate of Akt, regulates the sprouting of axons and the migration of neural progenitor cells during early postnatal-stage neurogenesis in the hippocampus. Here, we show that Girdin is highly expressed in human glioblastoma (GBM). Stable Girdin knockdown in isolated GBM stem cells resulted in decreased expression of stem cell markers, including CD133, induced multilineage neural differentiation, and inhibited in vitro cell motility, ex vivo invasion, sphere-forming capacity and in vivo tumor formation. Furthermore, exogenous expression of the Akt-binding domain of Girdin, which competitively inhibits its Akt-mediated phosphorylation, diminished the expression of stem cell markers, SOX2 and nestin, and migration on the brain slice and induced the expression of neural differentiation markers glial fibrillary acidic protein/bIII Tubulin. Our results reveal that Girdin is required for GBM-initiating stem cells to sustain the stemness and invasive properties.

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Section: Discussionmentioning

confidence: 99%

Section: Girdin Depletion Induces Differentiation From Gbm Stem Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Girdin maintains the stemness of glioblastoma stem cells

et al. 2011

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“…The VECTASTAIN ABC kit (Vector) and Envision kit/HRP (diaminobenzidine; DAKO) were used in each immunohistochemical analysis with counterstained hematoxylin. Immunohistochemical estimation of the percentage of positive SGNs detected by antibodies was calculated using the software program WinROOF (Mitani Corp.), as previously reported (34). In brief, the number of immunohistochemically positive SGNs was divided by the total number of SGNs in each Rosenthal's canal from three or four mice for each mouse strain.…”

Section: Methodsmentioning

confidence: 99%

c-Ret–mediated hearing loss in mice with Hirschsprung disease

Ohgami

Ida-Eto

Shimotake

et al. 2010

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

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A significantly increased risk for dominant sensorineural deafness in patients who have Hirschsprung disease (HSCR) caused by endothelin receptor type B and SOX10 has been reported. Despite the fact that c-RET is the most frequent causal gene of HSCR, it has not been determined whether impairments of c-Ret and c-RET cause congenital deafness in mice and humans. Here, we show that impaired phosphorylation of c-Ret at tyrosine 1062 causes HSCR-linked syndromic congenital deafness in c-Ret knockin (KI) mice. The deafness involves neurodegeneration of spiral ganglion neurons (SGNs) with not only impaired phosphorylation of Akt and NF-κB but decreased expression of calbindin D28k in inner ears. The congenital deafness involving neurodegeneration of SGNs in c-Ret KI mice was rescued by introducing constitutively activated RET. Taken together with our results for three patients with congenital deafness with c-RET-mediated severe HSCR, our results indicate that c-Ret and c-RET are a deafness-related molecule in mice and humans. spiral ganglion neuron | syndromic congenital deafness | tyrosine kinase A bout 30% of the 120 million people worldwide who suffer from congenital (early-onset) hearing loss are syndromic, and the remaining 70% are nonsyndromic (1-3). To elucidate the etiologies for the hearing losses, inner ears have been morphologically investigated as one of the target tissues. The inner ears contain the organ of Corti and the stria vascularis. The stria vascularis serves to maintain the endolymph potential. The organ of Corti, which consists of two kinds of sensory cells (inner hair cells and outer hair cells) is responsible for mechanotransduction, by which sound impulses are converted into neural impulses. Auditory information from the sensory cells is transmitted to spiral ganglion neurons (SGNs) as the primary carrier, followed by eventual transmission to the auditory cortex (1, 2

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“…Genetic analysis and abnormal expression level in schizophrenic patients [73,74] support the strong linkage between DISC1 and schizophrenia. Interestingly, DISC1 is involved in several neuronal functions such as neuronal migration, neurite outgrowth and synaptic plasticity, which are essential processes in neurogenesis and neurodevelopment [11,76]. In transgenic mice with Disc1 (mouse orthology of DISC1) mutation, working memory was decreased [77].…”

Section: Neurogenesis and Schizophreniamentioning

confidence: 99%

Neurogenic hypothesis and psychiatric disorders

Lau

Lee

2013

Chin. Sci. Bull.

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Psychiatric illness, such as affective disorders, anxiety disorders and schizophrenia, exerts exceptional personal burden on affected individuals. Although not physically noticeable, these disorders cost enormously on ones' family and society. Currently pharmaceutical and psychological treatments are generally accepted as effective for psychiatric disorders, while the exact mechanisms underlying the treatment efficacy, etiology and neurobiology of the disorders remain elusive. In the past decade, "neurogenic hypothesis" emerged as an attempt to explain the nature of psychiatric illness. The origination of the hypothesis is based on several pre-clinical and clinical observations. First, stress, which is a common risk factor of the disorders, was found to suppress neurogenesis; second, treatment for the illnesses like antidepressants and antipsychotics were shown to improve neurogenesis and behavioral deficits simultaneously; and third, the therapeutic effect of antidepressants was abolished in animal models when neurogenesis was blocked. Increasing efforts were invested to determine whether neurogenesis is a key to the understanding and treatment of psychiatric disorders, although contrasting results are also found and thus the importance of neurogenesis remains a matter of debate. The present chapter will discuss the recent findings about the involvement of neurogenesis in major depression, anxiety disorders and schizophrenia, and whether neurogenesis would be a potential target for development of the treatment in the future.neurogenesis, psychiatric disorders, major depression, schizophrenia, anxiety disorder, hippocampus, amygdala, subventricular zone Citation:

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Roles of Disrupted-In-Schizophrenia 1-Interacting Protein Girdin in Postnatal Development of the Dentate Gyrus

Cited by 168 publications

References 41 publications

Girdin maintains the stemness of glioblastoma stem cells

Girdin maintains the stemness of glioblastoma stem cells

c-Ret–mediated hearing loss in mice with Hirschsprung disease

Neurogenic hypothesis and psychiatric disorders

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