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https://www.readbyqxmd.com/read/28912643/decreased-glial-gaba-and-tonic-inhibition-in-cerebellum-of-mouse-model-for-attention-deficit-hyperactivity-disorder-adhd
#1
Yoo Sung Kim, Junsung Woo, C Justin Lee, Bo-Eun Yoon
About 5~12% of school-aged children suffer from the Attention-Deficit/Hyperactivity Disorder (ADHD). However, the core mechanism of ADHD remains unclear. G protein-coupled receptor kinase-interacting protein-1 (GIT1) has recently been reported to be associated with ADHD in human and the genetic deletion of GIT1 result in ADHD-like behaviors in mice. Mice lacking GIT1 shows a shift in neuronal excitation/inhibition (E/I) balance. However, the pricise mechanism for E/I imbalance and the role of neuron-glia interaction in GIT1 knockout (KO) mice have not been studied...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28759023/mecp2-a-target-of-mir-638-facilitates-gastric-cancer-cell-proliferation-through-activation-of-the-mek1-2-erk1-2-signaling-pathway-by-upregulating-git1
#2
L Y Zhao, D D Tong, M Xue, H L Ma, S Y Liu, J Yang, Y X Liu, B Guo, L Ni, L Y Liu, Y N Qin, L M Wang, X G Zhao, C Huang
Methyl-CpG binding protein 2 (MeCP2) is involved in the carcinogenesis and progression of multiple types of cancer. However, its precise role in gastric cancer (GC) and the relevant molecular mechanism remain unknown. In the present study, we found that miR-638 levels were lower in GC tissues and GC cell lines than in adjacent normal tissues and normal gastric epithelial cell lines, respectively. Low miR-638 levels were associated with poor tumor differentiation, tumor size and lymph node metastasis. MeCP2 expression levels were higher in GC tissues than in adjacent normal tissues...
July 31, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28754105/git1-gene-deletion-delays-chondrocyte-differentiation-and-healing-of-tibial-plateau-fracture-through-suppressing-proliferation-and-apoptosis-of-chondrocyte
#3
Peng Chen, Wan-Li Gu, Ming-Zhi Gong, Jun Wang, Dong-Qing Li
BACKGROUND: Although tibial plateau fracture is an uncommon injury, its regulation is challenging and there are some influencing factors, including the effects of severe bone displacement, depression and cancellous bone cartilage, and inevitable cartilage damage. And GIT1 plays an important role in bone mass and 78 osteoblast cell migration. METHODS: The study used 72 C57/BL6 mice. A tibial plateau fracture model was established by using mice with the same number of GIT1 gene deletions (the experimental group) and their wild-type littermates (the control group)...
July 28, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28600779/the-landscape-of-genetic-diseases-in-saudi-arabia-based-on-the-first-1000-diagnostic-panels-and-exomes
#4
Dorota Monies, Mohamed Abouelhoda, Moeenaldeen AlSayed, Zuhair Alhassnan, Maha Alotaibi, Husam Kayyali, Mohammed Al-Owain, Ayaz Shah, Zuhair Rahbeeni, Mohammad A Al-Muhaizea, Hamad I Alzaidan, Edward Cupler, Saeed Bohlega, Eissa Faqeih, Maha Faden, Banan Alyounes, Dyala Jaroudi, Ewa Goljan, Hadeel Elbardisy, Asma Akilan, Renad Albar, Hesham Aldhalaan, Shamshad Gulab, Aziza Chedrawi, Bandar K Al Saud, Wesam Kurdi, Nawal Makhseed, Tahani Alqasim, Heba Y El Khashab, Hamoud Al-Mousa, Amal Alhashem, Imaduddin Kanaan, Talal Algoufi, Khalid Alsaleem, Talal A Basha, Fathiya Al-Murshedi, Sameena Khan, Adila Al-Kindy, Maha Alnemer, Sami Al-Hajjar, Suad Alyamani, Hasan Aldhekri, Ali Al-Mehaidib, Rand Arnaout, Omar Dabbagh, Mohammad Shagrani, Dieter Broering, Maha Tulbah, Amal Alqassmi, Maisoon Almugbel, Mohammed AlQuaiz, Abdulaziz Alsaman, Khalid Al-Thihli, Raashda A Sulaiman, Wajeeh Al-Dekhail, Abeer Alsaegh, Fahad A Bashiri, Alya Qari, Suzan Alhomadi, Hisham Alkuraya, Mohammed Alsebayel, Muddathir H Hamad, Laszlo Szonyi, Faisal Abaalkhail, Sulaiman M Al-Mayouf, Hamad Almojalli, Khalid S Alqadi, Hussien Elsiesy, Taghreed M Shuaib, Mohammed Zain Seidahmed, Ibraheem Abosoudah, Hana Akleh, Abdulaziz AlGhonaium, Turki M Alkharfy, Fuad Al Mutairi, Wafa Eyaid, Abdullah Alshanbary, Farrukh R Sheikh, Fahad I Alsohaibani, Abdullah Alsonbul, Saeed Al Tala, Soher Balkhy, Randa Bassiouni, Ahmed S Alenizi, Maged H Hussein, Saeed Hassan, Mohamed Khalil, Brahim Tabarki, Saad Alshahwan, Amira Oshi, Yasser Sabr, Saad Alsaadoun, Mustafa A Salih, Sarar Mohamed, Habiba Sultana, Abdullah Tamim, Moayad El-Haj, Saif Alshahrani, Dalal K Bubshait, Majid Alfadhel, Tariq Faquih, Mohamed El-Kalioby, Shazia Subhani, Zeeshan Shah, Nabil Moghrabi, Brian F Meyer, Fowzan S Alkuraya
In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants...
August 2017: Human Genetics
https://www.readbyqxmd.com/read/28362242/arf-gaps-a-family-of-proteins-with-disparate-functions-that-converge-on-a-common-structure-the-integrin-adhesion-complex
#5
Teresa Vitali, Sofia Girald-Berlingeri, Paul A Randazzo, Pei-Wen Chen
ADP-ribosylation factors (Arfs) are members of the Ras GTPase superfamily. The function of Arfs is dependent on GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. Arf GAPs have been shown to be present in integrin adhesion complexes, which include focal adhesions. Integrin adhesion complexes are composed of integrins, scaffolding proteins and signaling proteins and regulate cell proliferation, survival, differentiation and migration...
March 31, 2017: Small GTPases
https://www.readbyqxmd.com/read/28325781/20-hete-signals-through-g-protein-coupled-receptor-gpr75-gq-to-affect-vascular-function-and-trigger-hypertension
#6
Victor Garcia, Ankit Gilani, Brian Shkolnik, Varunkumar Pandey, Frank Fan Zhang, Rambabu Dakarapu, Shyam K Gandham, N Rami Reddy, Joan P Graves, Artiom Gruzdev, Darryl C Zeldin, Jorge H Capdevila, John R Falck, Michal Laniado Schwartzman
RATIONALE: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction, and vascular diseases. OBJECTIVE: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists...
May 26, 2017: Circulation Research
https://www.readbyqxmd.com/read/28101188/mir-125a-3p-targetedly-regulates-git1-expression-to-inhibit-osteoblastic-proliferation-and-differentiation
#7
Xiao-Mei Tu, Yang-Lin Gu, Guo-Qin Ren
Osteoblasts are a prerequisite for osteogenesis and bone formation, and play a key role in metabolic balance, growth, development and wound repair. G protein-coupled receptor kinase interacting protein 1 (GIT1) and a series of miRNAs are known to have important effects in the growth and migration of osteoblasts, but little is known about micro RNAs (miRNAs) targeting GIT1. The present study found that miR-125a-3p has matching sites on GIT1. In the osteoblastic differentiation process of human bone marrow-derived mesenchymal stem cells (HMSCs), the expression of miR-125a-3p was suppressed compared with that in non-differentiating (HMSCs) while the expression of GIT1 showed a gradual and significant increase...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28087248/corrigendum-to-git1-betapix-signaling-proteins-and-pak1-kinase-regulate-microtubule-nucleation-biochim-biophys-acta-1863-6pa-2016-1282-1297
#8
Markéta Černohorská, Vadym Sulimenko, Zuzana Hájková, Tetyana Sulimenko, Vladimíra Sládková, Stanislav Vinopal, Eduarda Dráberová, Pavel Dráber
No abstract text is available yet for this article.
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#9
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27922692/mir-195-inhibits-the-proliferation-and-migration-of-chondrocytes-by-targeting-git1
#10
Yang-Lin Gu, Xiao-Xu Rong, Li-Ting Wen, Guo-Xing Zhu, Ming-Quan Qian
Previous studies have demonstrated that G-protein coupled receptor kinase interacting protein-1 (GIT1) and microRNAs (miRNAs) serve an important role in chondrocyte proliferation and migration. However, a limited number of studies conducted thus far have investigated the association between GIT1 and miRNAs. In the present study, putative miR‑195 binding sites in the GIT1 3'‑untranslated region were identified using common bioinformatic algorithms (miRanda, TargetScan, miRBase and miRWalk), and it was demonstrated that they may be involved in regulating GIT1 expression...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27698902/microrna-34c-suppresses-breast-cancer-migration-and-invasion-by-targeting-git1
#11
Wei-Yang Tao, Chun-Yang Wang, Yong-Hui Sun, Yong-Hui Su, Da Pang, Guo-Qiang Zhang
Abnormal expression of microRNAs plays important role in tumor metastasis. Migration and invasion of cancer cells accord for the metastasis and deterioration of breast cancer. However, the regulatory role of microRNAs in the invasion and migration of breast cancer cells has not completely understood yet. Here we found that microRNA-34c (miR-34c) was significantly downregulated in metastatic tissue of breast cancer. In vitro study showed that miR-34c negatively regulated GIT1 protein expression by binding to the 3'UTR of GIT1 mRNA...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27457813/functional-analysis-of-rare-variants-found-in-schizophrenia-implicates-a-critical-role-for-git1-pak3-signaling-in-neuroplasticity
#12
M J Kim, J Biag, D M Fass, M C Lewis, Q Zhang, M Fleishman, S P Gangwar, M Machius, M Fromer, S M Purcell, S A McCarroll, G Rudenko, R T Premont, E M Scolnick, S J Haggarty
Although the pathogenesis of schizophrenia (SCZ) is proposed to involve alterations of neural circuits via synaptic dysfunction, the underlying molecular mechanisms remain poorly understood. Recent exome sequencing studies of SCZ have uncovered numerous single-nucleotide variants (SNVs); however, the majority of these SNVs have unknown functional consequences, leaving their disease relevance uncertain. Filling this knowledge gap requires systematic application of quantitative and scalable assays to assess known and novel biological functions of genes...
March 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27363808/indexing-effects-of-copy-number-variation-on-genes-involved-in-developmental-delay
#13
Mohammed Uddin, Giovanna Pellecchia, Bhooma Thiruvahindrapuram, Lia D'Abate, Daniele Merico, Ada Chan, Mehdi Zarrei, Kristiina Tammimies, Susan Walker, Matthew J Gazzellone, Thomas Nalpathamkalam, Ryan K C Yuen, Koenraad Devriendt, Géraldine Mathonnet, Emmanuelle Lemyre, Sonia Nizard, Mary Shago, Ann M Joseph-George, Abdul Noor, Melissa T Carter, Grace Yoon, Peter Kannu, Frédérique Tihy, Erik C Thorland, Christian R Marshall, Janet A Buchanan, Marsha Speevak, Dimitri J Stavropoulos, Stephen W Scherer
A challenge in clinical genomics is to predict whether copy number variation (CNV) affecting a gene or multiple genes will manifest as disease. Increasing recognition of gene dosage effects in neurodevelopmental disorders prompted us to develop a computational approach based on critical-exon (highly expressed in brain, highly conserved) examination for potential etiologic effects. Using a large CNV dataset, our updated analyses revealed significant (P < 1.64 × 10(-15)) enrichment of critical-exons within rare CNVs in cases compared to controls...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27340174/proteomic-analysis-reveals-git1-as-a-novel-mtor-complex-component-critical-for-mediating-astrocyte-survival
#14
Laura J Smithson, David H Gutmann
As a critical regulator of cell growth, the mechanistic target of rapamycin (mTOR) protein operates as part of two molecularly and functionally distinct complexes. Herein, we demonstrate that mTOR complex molecular composition varies in different somatic tissues. In astrocytes and neural stem cells, we identified G-protein-coupled receptor kinase-interacting protein 1 (GIT1) as a novel mTOR-binding protein, creating a unique mTOR complex lacking Raptor and Rictor. Moreover, GIT1 binding to mTOR is regulated by AKT activation and is essential for mTOR-mediated astrocyte survival...
June 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27247625/a-novel-de-novo-microdeletion-at-17q11-2-adjacent-to-nf1-gene-associated-with-developmental-delay-short-stature-microcephaly-and-dysmorphic-features
#15
Bobo Xie, Xin Fan, Yaqin Lei, Rongyu Chen, Jin Wang, Chunyun Fu, Shang Yi, Jingsi Luo, Shujie Zhang, Qi Yang, Shaoke Chen, Yiping Shen
BACKGROUND: Microdeletions at 17q11.2 often encompass NF1 gene, is the cause for NF1 microdeletion syndrome. Microdeletion at 17q11.2 without the involvement of NF1 gene is rarely reported. CASE PRESENTATION: Here we reported a patient carrying a novel de novo deletion at 17q11.2 adjacent to NF1 gene, who presented with developmental delay, short stature, postnatal microcephaly, underweight and dysmorphic features including flat facial profile, dolicocephaly, hypertelorism, short philtrum, flat nasal bridge and posteriorly rotated and low set ears...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27220359/effects-of-platelet-derived-growth-factor-on-chondrocyte-proliferation-migration-and-apoptosis-via-regulation-of-git1-expression
#16
Guang-Zong Zhao, Long-Qiang Zhang, Yao Liu, Jun Fang, Hua-Zhuang Li, Ke-Hai Gao, Yun-Zhen Chen
The formation of fibrocartilage, cartilaginous and bony calluses is vital for bone healing following a fracture. Fibroblasts, chondrocytes and osteoblasts are critical functional cells that are involved in these three processes, respectively. Platelet‑derived growth factor (PDGF), a growth factor that is released from platelet particles and appears during the early stages at the site of fractures, is essential in bone healing via regulation of cell proliferation and differentiation. However, the effects of PDGF on the chondrocytes remain unclear...
July 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27182061/expanding-functions-of-git-arf-gtpase-activating-proteins-pix-rho-guanine-nucleotide-exchange-factors-and-git-pix-complexes
#17
REVIEW
Wu Zhou, Xiaobo Li, Richard T Premont
The GIT proteins, GIT1 and GIT2, are GTPase-activating proteins (inactivators) for the ADP-ribosylation factor (Arf) small GTP-binding proteins, and function to limit the activity of Arf proteins. The PIX proteins, α-PIX and β-PIX (also known as ARHGEF6 and ARHGEF7, respectively), are guanine nucleotide exchange factors (activators) for the Rho family small GTP-binding protein family members Rac1 and Cdc42. Through their multi-domain structures, GIT and PIX proteins can also function as signaling scaffolds by binding to numerous protein partners...
May 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27127481/git1-enhances-neurite-outgrowth-by-stimulating-microtubule-assembly
#18
Yi-Sheng Li, Li-Xia Qin, Jie Liu, Wei-Liang Xia, Jian-Ping Li, Hai-Lian Shen, Wei-Qiang Gao
GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment...
March 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27038336/p21-activated-kinase-pak-regulates-airway-smooth-muscle-contraction-by-regulating-paxillin-complexes-that-mediate-actin-polymerization
#19
Wenwu Zhang, Youliang Huang, Susan J Gunst
KEY POINTS: In airway smooth muscle, tension development caused by a contractile stimulus requires phosphorylation of the 20 kDa myosin light chain (MLC), which activates crossbridge cycling and the polymerization of a pool of submembraneous actin. The p21-activated kinases (Paks) can regulate the contractility of smooth muscle and non-muscle cells, and there is evidence that this occurs through the regulation of MLC phosphorylation. We show that Pak has no effect on MLC phosphorylation during the contraction of airway smooth muscle, and that it regulates contraction by mediating actin polymerization...
September 1, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27012601/git1-%C3%AE-pix-signaling-proteins-and-pak1-kinase-regulate-microtubule-nucleation
#20
Markéta Černohorská, Vadym Sulimenko, Zuzana Hájková, Tetyana Sulimenko, Vladimíra Sládková, Stanislav Vinopal, Eduarda Dráberová, Pavel Dráber
Microtubule nucleation from γ-tubulin complexes, located at the centrosome, is an essential step in the formation of the microtubule cytoskeleton. However, the signaling mechanisms that regulate microtubule nucleation in interphase cells are largely unknown. In this study, we report that γ-tubulin is in complexes containing G protein-coupled receptor kinase-interacting protein 1 (GIT1), p21-activated kinase interacting exchange factor (βPIX), and p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) in various cell lines...
June 2016: Biochimica et Biophysica Acta
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