Chimaerins: GAPs that bridge diacylglycerol signalling and the small G-protein Rac

2007 ◽  
Vol 403 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Chengfeng Yang ◽  
Marcelo G. Kazanietz
Keyword(s):  
G Protein ◽  
Rho Gtpase ◽  
System Development ◽  
Tumour Progression ◽  
Biological Properties ◽  
Nervous System Development ◽  
Small Gtpase ◽  
Gtpase Activating Proteins ◽  
Tumour Promoters ◽  
The Central Nervous System

Chimaerins are the only known RhoGAPs (Rho GTPase-activating proteins) that bind phorbol ester tumour promoters and the lipid second messenger DAG (diacylglycerol), and show specific GAP activity towards the small GTPase Rac. This review summarizes our knowledge of the structure, biochemical and biological properties of chimaerins. Recent findings have established that chimaerins are regulated by tyrosine kinase and GPCRs (G-protein-coupled receptors) via PLC (phospholipase C) activation and DAG generation to promote Rac inactivation. The finding that chimaerins, along with some other proteins, are receptors for DAG changed the prevalent view that PKC (protein kinase C) isoenzymes are the only cellular molecules regulated by DAG. In addition, vigorous recent studies have begun to decipher the critical roles of chimaerins in the central nervous system, development and tumour progression.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

scholarly journals Incorporation of 5-Bromo-2′-deoxyuridine into DNA and Proliferative Behavior of Cerebellar Neuroblasts: All That Glitters Is Not Gold

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1453
Author(s):  
Joaquín Martí-Clúa
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Current Data ◽  
Cellular Mechanisms ◽  
Dividing Cells ◽  
The Central Nervous System ◽  
Repeated Doses ◽  
Pyrimidine Analog

The synthetic halogenated pyrimidine analog, 5-bromo-2′-deoxyuridine (BrdU), is a marker of DNA synthesis. This exogenous nucleoside has generated important insights into the cellular mechanisms of the central nervous system development in a variety of animals including insects, birds, and mammals. Despite this, the detrimental effects of the incorporation of BrdU into DNA on proliferation and viability of different types of cells has been frequently neglected. This review will summarize and present the effects of a pulse of BrdU, at doses ranging from 25 to 300 µg/g, or repeated injections. The latter, following the method of the progressively delayed labeling comprehensive procedure. The prenatal and perinatal development of the cerebellum are studied. These current data have implications for the interpretation of the results obtained by this marker as an index of the generation, migration, and settled pattern of neurons in the developing central nervous system. Caution should be exercised when interpreting the results obtained using BrdU. This is particularly important when high or repeated doses of this agent are injected. I hope that this review sheds light on the effects of this toxic maker. It may be used as a reference for toxicologists and neurobiologists given the broad use of 5-bromo-2′-deoxyuridine to label dividing cells.

Pain and immunity

2021 ◽  
pp. 67-71
Author(s):  
Simon Beggs
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Early Life ◽  
System Development ◽  
Later Life ◽  
Nervous System Development ◽  
Neuronal Function ◽  
Neuronal Homeostasis ◽  
Neuroimmune Interactions ◽  
The Central Nervous System

The central nervous system (CNS) and immune system are inextricably linked. The complexity of their interactions is still being unraveled, but the list of processes mediated wholly or in part by neuroimmune interactions continues to grow. The influence of the immune system is crucial for normal nervous system development both pre- and postnatally, for maintaining neuronal homeostasis in the mature CNS and modulating synaptic plasticity. Aberrations in this crosstalk have been implicated in many neurodevelopmental and psychiatric disorders. It is not feasible to explore neuronal function at any point in the lifespan, in health or disease, without considering the influence of the immune system. In the adult animal it is now well established that pain chronicity is maintained by immune influence upon the neuronal nociceptive system, although, fascinatingly, there is now evidence for a marked sexual dimorphism in how the immune and nervous systems interact. This holds true for pain in early life, where the two still-developing systems provide a very different environment to mediate nociception and pain. Of particular interest is how the immune system and sex interact to early life painful events to prime pain responses in later life.

scholarly journals Drosophila GoLoco-Protein Pins Is a Target of Gαo-mediated G Protein–coupled Receptor Signaling

2009 ◽  
Vol 20 (17) ◽  
pp. 3865-3877 ◽  
Author(s):  
Damir Kopein ◽  
Vladimir L. Katanaev
Keyword(s):  
G Protein ◽  
System Development ◽  
Nervous System Development ◽  
G Protein Coupled Receptors ◽  
Guanine Nucleotide ◽  
Receptor Signaling ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Necessary And Sufficient ◽  
G Protein Coupled

G protein–coupled receptors (GPCRs) transduce their signals through trimeric G proteins, inducing guanine nucleotide exchange on their Gα-subunits; the resulting Gα-GTP transmits the signal further inside the cell. GoLoco domains present in many proteins play important roles in multiple trimeric G protein–dependent activities, physically binding Gα-subunits of the Gαi/o class. In most cases GoLoco binds exclusively to the GDP-loaded form of the Gα-subunits. Here we demonstrate that the poly-GoLoco–containing protein Pins of Drosophila can bind to both GDP- and GTP-forms of Drosophila Gαo. We identify Pins GoLoco domain 1 as necessary and sufficient for this unusual interaction with Gαo-GTP. We further pinpoint a lysine residue located centrally in this domain as necessary for the interaction. Our studies thus identify Drosophila Pins as a target of Gαo-mediated GPCR receptor signaling, e.g., in the context of the nervous system development, where Gαo acts downstream from Frizzled and redundantly with Gαi to control the asymmetry of cell divisions.

Neuronal Excitability in Epileptogenic Zones Regulated by the Wnt/ Β-Catenin Pathway

2020 ◽  
Vol 19 (1) ◽  
pp. 2-11 ◽  
Author(s):  
Carmen Rubio ◽  
Elisa Taddei ◽  
Jorge Acosta ◽  
Verónica Custodio ◽  
Carlos Paz
Keyword(s):  
Neuronal Excitability ◽  
System Development ◽  
Wnt Signaling Pathway ◽  
Epileptic Seizures ◽  
Epileptic Activity ◽  
Nervous System Development ◽  
Hippocampal Neurogenesis ◽  
Mitochondrial Regulation ◽  
The Central Nervous System ◽  
And Function

: Epilepsy is a neurological disorder that involves abnormal and recurrent neuronal discharges, producing epileptic seizures. Recently, it has been proposed that the Wnt signaling pathway is essential for the central nervous system development and function because it modulates important processes such as hippocampal neurogenesis, synaptic clefting, and mitochondrial regulation. Wnt/β- catenin signaling regulates changes induced by epileptic seizures, including neuronal death. Several genetic studies associate Wnt/β-catenin signaling with neuronal excitability and epileptic activity. Mutations and chromosomal defects underlying syndromic or inherited epileptic seizures have been identified. However, genetic factors underlying the susceptibility of an individual to develop epileptic seizures have not been fully studied yet. In this review, we describe the genes involved in neuronal excitability in epileptogenic zones dependent on the Wnt/β-catenin pathway.

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