関: guanine nucleotide exchange factors

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1. 小児におけるてんかん症候群 epilepsy syndromes in children
2. けいれんの臨床的特徴および評価 clinical features and evaluation of febrile seizures
3. 国際抗てんかん連盟（ILAE）によるてんかん発作およびてんかんの分類 ilae classification of seizures and epilepsy
4. 痙攣発作およびてんかんの病態生理 pathophysiology of seizures and epilepsy
5. 小児におけるてんかん重積状態の臨床的特徴および合併症 clinical features and complications of status epilepticus in children

English Journal

StarD13 is a tumor suppressor in breast cancer that regulates cell motility and invasion.

Hanna S1, Khalil B1, Nasrallah A1, Saykali BA1, Sobh R2, Nasser S2, El-Sibai M1.Author information 1Department of Natural Sciences, The Lebanese American University, Beirut 1102 2801, Lebanon.2School of Medicine, The Lebanese American University, Beirut 1102 2801, Lebanon.AbstractBreast cancer is one of the most commonly diagnosed cancers in women around the world. In general, the more aggressive the tumor, the more rapidly it grows and the more likely it metastasizes. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in breast cancer cell motility and metastasis. The switch between active GTP-bound and inactive GDP-bound state is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and guanine-nucleotide dissociation inhibitors (GDIs). We studied the role of StarD13, a recently identified Rho-GAP that specifically inhibits the function of RhoA and Cdc42. We aimed to investigate its role in breast cancer proliferation and metastasis. The levels of expression of this Rho-GAP in tumor tissues of different grades were assayed using immunohistochemistry. We observed that, while the level of StarD13 expression decreases in cancer tissues compared to normal tissues, it increases as the grade of the tumor increased. This was consistent with the fact that although StarD13 was indeed a tumor suppressor in our breast cancer cells, as seen by its effect on cell proliferation, it was needed for cancer cell motility. In fact, StarD13 knockdown resulted in an inhibition of cell motility and cells were not able to detach their tail and move forward. Our study describes, for the first time, a tumor suppressor that plays a positive role in cancer motility.
International journal of oncology.Int J Oncol.2014 May;44(5):1499-511. doi: 10.3892/ijo.2014.2330. Epub 2014 Mar 7.
Breast cancer is one of the most commonly diagnosed cancers in women around the world. In general, the more aggressive the tumor, the more rapidly it grows and the more likely it metastasizes. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in breast cancer c
PMID 24627003

A Novel GABRG2 mutation, p.R136*, in a family with GEFS+ and extended phenotypes.

Johnston AJ1, Kang JQ2, Shen W2, Pickrell WO1, Cushion TD3, Davies JS3, Baer K3, Mullins JG4, Hammond CL5, Chung SK5, Thomas RH1, White C6, Smith PE7, Macdonald RL2, Rees MI8.Author information 1Wales Epilepsy Research Network, Institute of Life Sciences, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK; Neurology and Molecular Neuroscience Research Group, Institute of Life Sciences, College of Medicine, Swansea University, Singleton 8PP, UK; Department of Neurology, University Hospital of Wales, Heath Park, Cardiff CF14 4X, UK.2Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232-8552, USA.3Neurology and Molecular Neuroscience Research Group, Institute of Life Sciences, College of Medicine, Swansea University, Singleton 8PP, UK.4Genome and Structural Bioinformatics, Institute of Life Sciences, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.5Wales Epilepsy Research Network, Institute of Life Sciences, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK; Neurology and Molecular Neuroscience Research Group, Institute of Life Sciences, College of Medicine, Swansea University, Singleton 8PP, UK.6Wales Epilepsy Research Network, Institute of Life Sciences, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK; Paediatric Neurology, Singleton Hospital, Abertawe Bro-Morgannwg University Health Board, Swansea SA2 8PP, UK.7Department of Neurology, University Hospital of Wales, Heath Park, Cardiff CF14 4X, UK.8Wales Epilepsy Research Network, Institute of Life Sciences, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK; Neurology and Molecular Neuroscience Research Group, Institute of Life Sciences, College of Medicine, Swansea University, Singleton 8PP, UK. Electronic address: m.i.rees@swansea.ac.uk.AbstractGenetic mutations in voltage-gated and ligand-gated ion channel genes have been identified in a small number of Mendelian families with genetic generalised epilepsies (GGEs). They are commonly associated with febrile seizures (FS), childhood absence epilepsy (CAE) and particularly with generalised or genetic epilepsy with febrile seizures plus (GEFS+). In clinical practice, despite efforts to categorise epilepsy and epilepsy families into syndromic diagnoses, many generalised epilepsies remain unclassified with a presumed genetic basis. During the systematic collection of epilepsy families, we assembled a cohort of families with evidence of GEFS+ and screened for variations in the γ2 subunit of the γ-aminobutyric acid (GABA) type A receptor gene (GABRG2). We detected a novel GABRG2(p.R136*) premature translation termination codon in one index-case from a two-generation nuclear family, presenting with an unclassified GGE, a borderline GEFS+ phenotype with learning difficulties and extended behavioural presentation. The GABRG2(p.R136*) mutation segregates with the febrile seizure component of this family's GGE and is absent in 190 healthy control samples. In vitro expression assays demonstrated that γ2(p.R136*) subunits were produced, but had reduced cell-surface and total expression. When γ2(p.R136*) subunits were co-expressed with α1 and β2 subunits in HEK 293T cells, GABA-evoked currents were reduced. Furthermore, γ2(p.R136*) subunits were highly-expressed in intracellular aggregations surrounding the nucleus and endoplasmic reticulum (ER), suggesting compromised receptor trafficking. A novel GABRG2(p.R136*) mutation extends the spectrum of GABRG2 mutations identified in GEFS+ and GGE phenotypes, causes GABAA receptor dysfunction, and represents a putative epilepsy mechanism.
Neurobiology of disease.Neurobiol Dis.2014 Apr;64:131-41. doi: 10.1016/j.nbd.2013.12.013. Epub 2014 Jan 7.
Genetic mutations in voltage-gated and ligand-gated ion channel genes have been identified in a small number of Mendelian families with genetic generalised epilepsies (GGEs). They are commonly associated with febrile seizures (FS), childhood absence epilepsy (CAE) and particularly with generalised o
PMID 24407264

Confirming an expanded spectrum of SCN2A mutations: a case series.

Matalon D, Goldberg E, Medne L, Marsh ED.Author information Division of Child Neurology, Departments of Pediatrics and Neurology, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA.AbstractMutations in sodium channel genes are highly associated with epilepsy. Mutation of SCN1A, the gene encoding the voltage gated sodium channel (VGSC) alpha subunit type 1 (Nav1.1), causes Dravet syndrome spectrum disorders. Mutations in SCN2A have been identified in patients with benign familial neonatal-infantile epilepsy (BFNIE), generalised epilepsy with febrile seizures plus (GEFS+), and a small number of reported cases of other infantile-onset severe intractable epilepsy. Here, we report three patients with infantile-onset severe intractable epilepsy found to have de novo mutations in SCN2A. While a causal role for these mutations cannot be directly established, these findings contribute to growing evidence that mutation of SCN2A is associated with a range of epilepsy phenotypes including severe infantile-onset epilepsy.
Epileptic disorders : international epilepsy journal with videotape.Epileptic Disord.2014 Mar 21. [Epub ahead of print]
Mutations in sodium channel genes are highly associated with epilepsy. Mutation of SCN1A, the gene encoding the voltage gated sodium channel (VGSC) alpha subunit type 1 (Nav1.1), causes Dravet syndrome spectrum disorders. Mutations in SCN2A have been identified in patients with benign familial neona
PMID 24659627

Japanese Journal

てんかんとイオンチャネルの機能異常

杉浦嘉泰
福島医学雑誌 65(2), 41-47, 2015-06
NAID 40020546263

Dravet症候群とGEFS+の遺伝子 : SCN1A遺伝子変異のスペクトラムと他の遺伝子 (AYUMI てんかんの遺伝学的診断)

石井敦士
医学のあゆみ 253(7), 561-567, 2015-05-16
NAID 40020457298

出芽酵母のメンブレントラフィックにおけるRab GTPaseネットワーク

長野真,十島純子,十島二朗
薬学雑誌. 乙号 135(3), 483-492, 2015
… In yeast, the secretory pathway is regulated by sequential activation and inactivation (the so-called Rab cascade) of three types of yeast Rab protein -Ypt1p, Ypt31p/32p and Sec4p -via specific guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). …
NAID 130004756514