The Human Rho-GEF Trio and Its Target GTPase RhoG Are Involved in the NGF Pathway, Leading to Neurite Outgrowth
| Autor: | Aubin Penna, Sylvie Diriong, Anne Debant, Anne Blangy, Soline Estrach, Philippe Fort, Susanne Schmidt |
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| Přispěvatelé: | Biologie et physiopathologie cutanées : expression génique, signalisation et thérapie, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherches de biochimie macromoléculaire (CRBM), Centre National de la Recherche Scientifique (CNRS)-IFR122-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Philippe, Fort |
| Jazyk: | angličtina |
| Předmět: |
rho GTP-Binding Proteins
RHOA MESH: rac GTP-Binding Proteins GTPase CDC42 [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics Phylogenetics and taxonomy PC12 Cells GTP Phosphohydrolases 0302 clinical medicine Nerve Growth Factor Guanine Nucleotide Exchange Factors MESH: Guanine Nucleotide Exchange Factors MESH: Animals Pseudopodia cdc42 GTP-Binding Protein MESH: Nerve Growth Factor MESH: Cell Size 0303 health sciences Microscopy Video biology Agricultural and Biological Sciences(all) [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis Cell Differentiation rac GTP-Binding Proteins Cell biology Guanine nucleotide exchange factor General Agricultural and Biological Sciences MESH: Cell Differentiation MESH: GTP Phosphohydrolases MESH: Mutation Neurite MESH: Rats Growth Cones [SDV.CAN]Life Sciences [q-bio]/Cancer General Biochemistry Genetics and Molecular Biology 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer [SDV.BID.SPT] Life Sciences [q-bio]/Biodiversity/Systematics Phylogenetics and taxonomy Neurites [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Animals Humans MESH: PC12 Cells Cell Size 030304 developmental biology MESH: Humans MESH: cdc42 GTP-Binding Protein Biochemistry Genetics and Molecular Biology(all) [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology MESH: Growth Cones Actin cytoskeleton MESH: rho GTP-Binding Proteins MESH: Neurites Rats MESH: Microscopy Video [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis MESH: Pseudopodia Mutation biology.protein Axon guidance RhoG 030217 neurology & neurosurgery |
| Zdroj: | Current Biology-CB Current Biology-CB, Elsevier, 2002, 12 (4), pp.307-312. ⟨10.1016/s0960-9822(02)00658-9⟩ Current Biology-CB, 2002, 12 (4), pp.307-312. ⟨10.1016/s0960-9822(02)00658-9⟩ |
| ISSN: | 0960-9822 1879-0445 |
| DOI: | 10.1016/S0960-9822(02)00658-9 |
| Popis: | Rho-GTPases control a wide range of physiological processes by regulating actin cytoskeleton dynamics [1]. Numerous studies on neuronal cell lines have established that Rac, Cdc42, and RhoG activate neurite extension, while RhoA mediates neurite retraction [2–5]. Guanine nucleotide exchange factors (GEFs) activate Rho-GTPases by accelerating GDP/GTP exchange [6]. Trio displays two Rho-GEF domains, GEFD1, activating the Rac pathway via RhoG, and GEFD2, acting on RhoA, and contains numerous signaling motifs whose contribution to Trio function has not yet been investigated [7–9]. Genetic analyses in Drosophila and in Caenorhabditis elegans indicate that Trio is involved in axon guidance and cell motility via a GEFD1-dependent process, suggesting that the activity of its Rho-GEFs is strictly regulated [10–14]. Here, we show that human Trio induces neurite outgrowth in PC12 cells in a GEFD1-dependent manner. Interestingly, the spectrin repeats and the SH3-1 domain of Trio are essential for GEFD1-mediated neurite outgrowth, revealing an unexpected role for these motifs in Trio function. Moreover, we demonstrate that Trio-induced neurite outgrowth is mediated by the GEFD1-dependent activation of RhoG, previously shown to be part of the NGF (nerve growth factor) pathway [4]. The expression of different Trio mutants interferes with NGF-induced neurite outgrowth, suggesting that Trio may be an upstream regulator of RhoG in this pathway. In addition, we show that Trio protein accumulates under NGF stimulation. Thus, Trio is the first identified Rho-GEF involved in the NGF-differentiation signaling. |
| Databáze: | OpenAIRE |
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