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The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases

Small GTPases participate in a broad range of cellular processes such as proliferation, differentiation, and migration. The exchange of GDP for GTP resulting in the activation of these GTPases is catalyzed by a group of enzymes called guanine nucleotide exchange factors (GEFs), of which two classes:...

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Autores principales: Droppelmann, Cristian A., Campos-Melo, Danae, Volkening, Kathryn, Strong, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159981/
https://www.ncbi.nlm.nih.gov/pubmed/25309324
http://dx.doi.org/10.3389/fncel.2014.00282
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author Droppelmann, Cristian A.
Campos-Melo, Danae
Volkening, Kathryn
Strong, Michael J.
author_facet Droppelmann, Cristian A.
Campos-Melo, Danae
Volkening, Kathryn
Strong, Michael J.
author_sort Droppelmann, Cristian A.
collection PubMed
description Small GTPases participate in a broad range of cellular processes such as proliferation, differentiation, and migration. The exchange of GDP for GTP resulting in the activation of these GTPases is catalyzed by a group of enzymes called guanine nucleotide exchange factors (GEFs), of which two classes: Dbl-related exchange factors and the more recently described dedicator of cytokinesis proteins family exchange factors. Increasingly, deregulation of normal GEF activity or function has been associated with a broad range of disease states, including neurodegeneration and neurodevelopmental disorders. In this review, we examine this evidence with special emphasis on the novel role of Rho guanine nucleotide exchange factor (RGNEF/p190RhoGEF) in the pathogenesis of amyotrophic lateral sclerosis. RGNEF is the first neurodegeneration-linked GEF that regulates not only RhoA GTPase activation but also functions as an RNA binding protein that directly acts with low molecular weight neurofilament mRNA 3′ untranslated region to regulate its stability. This dual role for RGNEF, coupled with the increasing understanding of the key role for GEFs in modulating the GTPase function in cell survival suggests a prominent role for GEFs in mediating a critical balance between cytotoxicity and neuroprotection which, when disturbed, contributes to neuronal loss.
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spelling pubmed-41599812014-10-10 The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases Droppelmann, Cristian A. Campos-Melo, Danae Volkening, Kathryn Strong, Michael J. Front Cell Neurosci Neuroscience Small GTPases participate in a broad range of cellular processes such as proliferation, differentiation, and migration. The exchange of GDP for GTP resulting in the activation of these GTPases is catalyzed by a group of enzymes called guanine nucleotide exchange factors (GEFs), of which two classes: Dbl-related exchange factors and the more recently described dedicator of cytokinesis proteins family exchange factors. Increasingly, deregulation of normal GEF activity or function has been associated with a broad range of disease states, including neurodegeneration and neurodevelopmental disorders. In this review, we examine this evidence with special emphasis on the novel role of Rho guanine nucleotide exchange factor (RGNEF/p190RhoGEF) in the pathogenesis of amyotrophic lateral sclerosis. RGNEF is the first neurodegeneration-linked GEF that regulates not only RhoA GTPase activation but also functions as an RNA binding protein that directly acts with low molecular weight neurofilament mRNA 3′ untranslated region to regulate its stability. This dual role for RGNEF, coupled with the increasing understanding of the key role for GEFs in modulating the GTPase function in cell survival suggests a prominent role for GEFs in mediating a critical balance between cytotoxicity and neuroprotection which, when disturbed, contributes to neuronal loss. Frontiers Media S.A. 2014-09-10 /pmc/articles/PMC4159981/ /pubmed/25309324 http://dx.doi.org/10.3389/fncel.2014.00282 Text en Copyright © 2014 Droppelmann, Campos-Melo, Volkening and Strong. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Droppelmann, Cristian A.
Campos-Melo, Danae
Volkening, Kathryn
Strong, Michael J.
The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases
title The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases
title_full The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases
title_fullStr The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases
title_full_unstemmed The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases
title_short The emerging role of guanine nucleotide exchange factors in ALS and other neurodegenerative diseases
title_sort emerging role of guanine nucleotide exchange factors in als and other neurodegenerative diseases
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159981/
https://www.ncbi.nlm.nih.gov/pubmed/25309324
http://dx.doi.org/10.3389/fncel.2014.00282
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