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https://www.readbyqxmd.com/read/27184948/morphological-and-behavioral-characterization-of-adult-mice-deficient-for-srgap3
#1
Jonathan Bertram, Leif Koschützke, Jörg P Pfannmöller, Jennifer Esche, Laura van Diepen, Andreas W Kuss, Bianca Hartmann, Dusan Bartsch, Martin Lotze, Oliver von Bohlen Und Halbach
SrGAP3 belongs to the family of Rho GTPase proteins. These proteins are thought to play essential roles in development and in the plasticity of the nervous system. SrGAP3-deficient mice have recently been created and approximately 10 % of these mice developed a hydrocephalus and died shortly after birth. The others survived into adulthood, but displayed neuroanatomical alteration, including increased ventricular size. We now show that SrGAP3-deficient mice display increased brain weight together with increased hippocampal volume...
October 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27113584/non-catalytic-roles-for-tet1-protein-negatively-regulating-neuronal-differentiation-through-srgap3-in-neuroblastoma-cells
#2
Jie Gao, Yue Ma, Hua-Lin Fu, Qian Luo, Zhen Wang, Yu-Huan Xiao, Hao Yang, Da-Xiang Cui, Wei-Lin Jin
The methylcytosine dioxygenases TET proteins (TET1, TET2, and TET3) play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA (valproic acid)-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neuronal differentiation of Neuro2a cells...
May 2016: Protein & Cell
https://www.readbyqxmd.com/read/26104135/srgap3-knockout-mice-display-enlarged-lateral-ventricles-and-specific-cilia-disturbances-of-ependymal-cells-in-the-third-ventricle
#3
Leif Koschützke, Jonathan Bertram, Bianca Hartmann, Dusan Bartsch, Martin Lotze, Oliver von Bohlen und Halbach
In several mouse models of mental retardation, ventricular enlargements have been observed. Mutation in the SrGAP3 gene residing on chromosome 3p25 has previously been associated with intellectual disability in humans. In addition, SrGAP3 is related to Rho-GAPs signaling pathways, which play essential roles in the development and plasticity of the nervous system. About 10 % of postnatal homozygous SrGAP3-deficient mice die due to hydrocephalus, whereas the remaining mice survive into adulthood but display enlarged ventricles...
August 2015: Cell and Tissue Research
https://www.readbyqxmd.com/read/25819436/a-single-pxxp-motif-in-the-c-terminal-region-of-srgap3-mediates-binding-to-multiple-sh3-domains
#4
Silvia Wuertenberger, Yvonne Groemping
The Slit-Robo GTPase-activating protein 3 (srGAP3) has been implicated in different critical aspects of neuronal development. These findings have mainly been based on the characterisation of the three conserved globular N-terminal domains, while the function of the C-terminal region (CTR) is still unknown. We show that this predicted unstructured region acts as an adaptor by binding to the endocytic proteins Amphiphysin, Endophilin-A2, Endophilin-A1, as well as the Ras signalling protein Grb2. All these interactions depend on a single proline-rich motif in the CTR and the Src-homology 3 domains of the binding partners...
April 28, 2015: FEBS Letters
https://www.readbyqxmd.com/read/25149377/srgap3-promotes-neurite-outgrowth-of-dorsal-root-ganglion-neurons-by-inactivating-rac1
#5
Quan-Peng Zhang, Hai-Ying Zhang, Xian-Fang Zhang, Jiu-Hong Zhao, Zhi-Jian Ma, Dan Zhao, Xi-Nan Yi
OBJECTIVE: To explore effect of srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons. METHODS: In this study, expression of Slit1 was observed predominantly in the glia, while expression of Robo2 and srGAP3 was detected in sensory neurons of postnatal rat cultured dorsal root ganglion (DRG). Furthermore, upregulation of srGAP3 following sciatic nerve transection was detected by immunohistochemistry and Western blotting. RESULTS: It was observed that inhibition of neurite outgrowth in cultured adult DRG neurons following treatment with anti-srGAP3 or anti-Robo2 was more effectively (1...
August 2014: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/24561795/a-link-between-the-nuclear-localized-srgap3-and-the-swi-snf-chromatin-remodeler-brg1
#6
Yun-Kai Dai, Yue Ma, Keng Chen, Ya-Jing Mi, Hua-Lin Fu, Da-Xiang Cui, Wei-Lin Jin
The Slit-Robo GTPase activating protein 3 (srGAP3) is an important modulator of actin cytoskeletal dynamics and has an important influence on a variety of neurodevelopmental processes. Mutations in the SRGAP3 gene on chromosome 3p25 have been found in patients with intellectual disability. Genome-wide association studies and behavioral assays of knockout mice had also revealed SRGAP3 as a risk gene for schizophrenia. We have recently shown that srGAP3 protein undergoes regulated shuttling between the cytoplasm and the nucleus during neuronal development...
May 2014: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/24300292/interstitial-3p25-deletion-in-a-patient-with-features-of-3p-deletion-syndrome-further-evidence-for-the-role-of-srgap3-in-mental-retardation
#7
Peter M Ellery, Richard J Ellis, Susan E Holder
No abstract text is available yet for this article.
January 2014: Clinical Dysmorphology
https://www.readbyqxmd.com/read/23505444/the-inverse-f-bar-domain-protein-srgap2-acts-through-srgap3-to-modulate-neuronal-differentiation-and-neurite-outgrowth-of-mouse-neuroblastoma-cells
#8
Yue Ma, Ya-Jing Mi, Yun-Kai Dai, Hua-Lin Fu, Da-Xiang Cui, Wei-Lin Jin
The inverse F-BAR (IF-BAR) domain proteins srGAP1, srGAP2 and srGAP3 are implicated in neuronal development and may be linked to mental retardation, schizophrenia and seizure. A partially overlapping expression pattern and highly similar protein structures indicate a functional redundancy of srGAPs in neuronal development. Our previous study suggests that srGAP3 negatively regulates neuronal differentiation in a Rac1-dependent manner in mouse Neuro2a cells. Here we show that exogenously expressed srGAP1 and srGAP2 are sufficient to inhibit valporic acid (VPA)-induced neurite initiation and growth in the mouse Neuro2a cells...
2013: PloS One
https://www.readbyqxmd.com/read/23311320/the-mental-retardation-associated-protein-srgap3-regulates-survival-proliferation-and-differentiation-of-rat-embryonic-neural-stem-progenitor-cells
#9
Haixia Lu, Qian Jiao, Yuanyuan Wang, Zhiqian Yang, Minjuan Feng, Li Wang, Xinlin Chen, Weilin Jin, Yong Liu
The mental retardation-associated protein, srGAP3 is highly expressed in neurogenic sites. It is thought to regulate the key aspects of neuronal development and functions. Little is known about the interaction between srGAP3 and immature neural stem cells/neural progenitor cells (NSCs/NPCs). In the current study, the expression of srGAP3 in NSCs/NPCs was detected. Then, survival, proliferation, differentiation, and morphological alteration of NSCs/NPCs were assessed after a lentivirus-mediated knockdown of srGAP3...
June 1, 2013: Stem Cells and Development
https://www.readbyqxmd.com/read/23127797/the-cellular-function-of-srgap3-and-its-role-in-neuronal-morphogenesis
#10
Claire Bacon, Volker Endris, Gudrun A Rappold
The Slit-Robo GTPase activating protein 3 (srGAP3) dynamically regulates cytoskeletal reorganisation through inhibition of the Rho GTPase Rac1 and interaction with actin remodelling proteins. SrGAP3-mediated reorganisation of the actin cytoskeleton is crucial for the normal development of dendritic spines and loss of srGAP3 leads to abnormal synaptic activity and impaired cognitive behaviours in mice, which is reminiscent of an association between disrupted srGAP3 and intellectual disability in humans. Additionally, srGAP3 has been implicated to act downstream of Slit-Robo signalling in commissural axons of the spinal cord...
June 2013: Mechanisms of Development
https://www.readbyqxmd.com/read/23108406/a-tumor-suppressor-role-for-srgap3-in-mammary-epithelial-cells
#11
A Lahoz, A Hall
srGAP3, a member of the Slit-Robo sub-family of Rho GTPase-activating proteins (Rho GAPs), controls actin and microtubule dynamics through negative regulation of Rac. Here, we describe a potential role for srGAP3 as a tumor suppressor in mammary epithelial cells. We show that RNAi-mediated depletion of srGAP3 promotes Rac dependent, anchorage-independent growth of partially transformed human mammary epithelial cells (HMECs). Furthermore, srGAP3 expression is absent, or significantly reduced in 7/10 breast cancer cell lines compared with normal HMECs...
October 2013: Oncogene
https://www.readbyqxmd.com/read/23074677/a-novel-microduplication-in-the-neurodevelopmental-gene-srgap3-that-segregates-with-psychotic-illness-in-the-family-of-a-cos-proband
#12
Nicole K A Wilson, Yohan Lee, Robert Long, Karen Hermetz, M Katharine Rudd, Rachel Miller, Judith L Rapoport, Anjené M Addington
Schizophrenia is a debilitating mental disorder affecting approximately 1% of the world's population. Childhood onset schizophrenia (COS), defined as onset before age 13, is a rare and severe form of the illness that may have more salient genetic influence. We identified a ~134 kb duplication spanning exons 2-4 of the Slit-Robo GTPase-activating protein 3 (SRGAP3) gene on chromosome 3p25.3 that tracks with psychotic illness in the family of a COS proband. Cloning and sequencing of the duplication junction confirmed that the duplication is tandem, and analysis of the resulting mRNA transcript suggests that the duplication would result in a frame shift mutation...
2011: Case Reports in Genetics
https://www.readbyqxmd.com/read/23040932/pure-partial-monosomy-3p-3p25-3-%C3%A2-pter-prenatal-diagnosis-and-array-comparative-genomic-hybridization-characterization
#13
Chih-Ping Chen, Yi-Ning Su, Chen-Yu Chen, Jun-Wei Su, Schu-Rern Chern, Dai-Dyi Town, Wayseen Wang
OBJECTIVE: The purpose of this case report is to present prenatal diagnosis and molecular cytogenetic characterization of pure partial monosomy 3p (3p25.3 → pter) by array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) on uncultured amniocytes. CASE REPORT: A 35-year-old, gravida 2, para 0, woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Her husband was 37 years of age...
September 2012: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/23007397/disruption-of-wave-associated-rac-gtpase-activating-protein-wrp-leads-to-abnormal-adult-neural-progenitor-migration-associated-with-hydrocephalus
#14
Il Hwan Kim, Benjamin R Carlson, Clifford C Heindel, Hyun Kim, Scott H Soderling
Hydrocephalus is the most common developmental disability and leading cause of brain surgery for children. Current treatments are limited to surgical intervention, as the factors that contribute to the initiation of hydrocephalus are poorly understood. Here, we describe the development of obstructive hydrocephalus in mice that are null for Wrp (Srgap3). Wrp is highly expressed in the ventricular stem cell niche, and it is a gene required for cytoskeletal organization and is associated with syndromic and psychiatric disorders in humans...
November 9, 2012: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22965684/interstitial-3p25-3-p26-1-deletion-in-a-patient-with-intellectual-disability
#15
Angelika Riess, Ute Grasshoff, Karin Schäferhoff, Michael Bonin, Olaf Riess, Veronka Horber, Andreas Tzschach
Interstitial deletions of the short arm of chromosome 3 are rare. We report on a 3-year-old girl with intellectual disability, muscular hypotonia, strabismus, and facial anomalies in whom an interstitial 1.24 Mb deletion in 3p25.3-p26.1 was detected by SNP array analysis. The deleted region harbors 11 RefSeq genes including CAV3 and SRGAP3/MEGAP, which had been associated with muscle disorders and intellectual disability, respectively. The deletion overlaps with a slightly larger deletion in a girl with a more complex phenotype including congenital heart defect and epilepsy, which indicates that haploinsufficiency of one or several of the genes in the deleted interval causes intellectual deficits, but not heart defects or epilepsy...
October 2012: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/22903836/microdeletion-on-3p25-in-a-patient-with-features-of-3p-deletion-syndrome
#16
Iskra T Peltekova, Athen Macdonald, Christine M Armour
The rare 3p deletion syndrome presents with a spectrum of anomalies caused by deletions of variable lengths within the short arm of chromosome 3. While most of these deletions involve the 3p terminus, interstitial deletions may also give rise to features of the syndrome. We have detected an interstitial deletion of 643 kb in a patient who displayed many of the typical 3p deletion features. This patient had a number of findings in common with a previously reported patient, who had a 1.6 Mb interstitial deletion, including cognitive handicap, seizures, and congenital heart defects...
October 2012: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/22820399/srgap3%C3%A2-%C3%A2-mice-present-a-neurodevelopmental-disorder-with-schizophrenia-related-intermediate-phenotypes
#17
Robert Waltereit, Uwe Leimer, Oliver von Bohlen Und Halbach, Jutta Panke, Sabine M Hölter, Lillian Garrett, Karola Wittig, Miriam Schneider, Camie Schmitt, Julia Calzada-Wack, Frauke Neff, Lore Becker, Cornelia Prehn, Sergej Kutscherjawy, Volker Endris, Claire Bacon, Helmut Fuchs, Valérie Gailus-Durner, Stefan Berger, Kai Schönig, Jerzy Adamski, Thomas Klopstock, Irene Esposito, Wolfgang Wurst, Martin Hrabe de Angelis, Gudrun Rappold, Thomas Wieland, Dusan Bartsch
Mutations in the SRGAP3 gene residing on chromosome 3p25 have previously been associated with intellectual disability. Genome-wide association studies have also revealed SRGAP3, together with genes from the same cellular network, as risk genes for schizophrenia. SRGAP3 regulates cytoskeletal dynamics through the RHO protein RAC1. RHO proteins are known to be involved in cytoskeletal reorganization during brain development to control processes such as synaptic plasticity. To elucidate the importance of SRGAP3 in brain development, we generated Srgap3-knockout mice...
November 2012: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/22467852/the-f-bar-domains-from-srgap1-srgap2-and-srgap3-regulate-membrane-deformation-differently
#18
Jaeda Coutinho-Budd, Vladimir Ghukasyan, Mark J Zylka, Franck Polleux
Coordination of membrane deformation and cytoskeletal dynamics lies at the heart of many biological processes critical for cell polarity, motility and morphogenesis. We have recently shown that Slit-Robo GTPase-activating protein 2 (srGAP2) regulates neuronal morphogenesis through the ability of its F-BAR domain to regulate membrane deformation and induce filopodia formation. Here, we demonstrate that the F-BAR domains of two closely related family members, srGAP1 and srGAP3 [designated F-BAR(1) and F-BAR(3), respectively] display significantly different membrane deformation properties in non-neuronal COS7 cells and in cortical neurons...
July 15, 2012: Journal of Cell Science
https://www.readbyqxmd.com/read/22271578/slit-robo-gtpase-activating-proteins-are-differentially-expressed-in-murine-dorsal-root-ganglia-modulation-by-peripheral-nerve-injury
#19
COMPARATIVE STUDY
Zhi-Bing Chen, Hai-Ying Zhang, Jiu-Hong Zhao, Wei Zhao, Dan Zhao, Lin-Feng Zheng, Xian-Fang Zhang, Xiao-Ping Liao, Xi-Nan Yi
The Slit-Robo GTPase-activating proteins (srGAPs) play an important role in neurite outgrowth and axon guidance; however, little is known about its role in nerve regeneration after injury. Here, we studied the expression of srGAPs in mouse dorsal root ganglia (DRG) following sciatic nerve transection (SNT) using morphometric and immunohistochemical techniques. Reverse transcriptase polymerase chain reaction and Western blot analysis indicated that srGAP1 and srGAP3, but not srGAP2, were expressed in normal adult DRG...
April 2012: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/22159416/srgap3-interacts-with-lamellipodin-at-the-cell-membrane-and-regulates-rac-dependent-cellular-protrusions
#20
Volker Endris, Lydia Haussmann, Elena Buss, Claire Bacon, Dusan Bartsch, Gudrun Rappold
SrGAP3/MEGAP is a member of the Slit-Robo GAP (srGAP) family and is implicated in repulsive axon guidance and neuronal migration through Slit-Robo-mediated signal transduction. Here we describe an inhibitory role of srGAP3 on actin dynamics, specifically on lamellipodia formation. We show that the F-BAR domain localizes srGAP3 to the leading edge of cellular protrusions whereas the SH3 domain is important for focal adhesion targeting. We report on a novel srGAP3 interaction partner, lamellipodin, which localizes with srGAP3 at the leading edge...
December 1, 2011: Journal of Cell Science
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