title: Deficiency of G3BP1, the stress granules assembly factor, results in abnormal synaptic plasticity and calcium homeostasis in neurons.
abstract: Ras-GAP SH3-domain-binding protein, G3BP, is an important component in the assembly of stress granules (SGs), which are cytoplasmic aggregates assembled following translational stress. To assess the physiological function of G3BP, we generated viable G3bp1-knockout (KO) mice, which demonstrated behavioral defects linked to the CNS-associated with ataxia phenotype. Immunohistochemistry pinpointed high expression of G3BP in the cytoplasm of hippocampal neurons and Purkinje cells of the cerebellum of wild-type mice. Also, electrophysiological measurements revealed that the absence of G3BP1 leads to an enhancement of short-term potentiation (STP) and long-term depression in the CA1 area of G3bp1 KO mice compared with wild-type mice. Consistently, G3BP1 deficiency in neurons leads to an increase in intracellular calcium and calcium release in response to (S)-3,5-Dihydroxyphenylglycine, a selective agonist of group I metabotropic glutamate receptors. These results show, for the first time, a requirement for G3BP1 in the control of neuronal plasticity and calcium homeostasis and further establish a direct link between SG formation and neurodegenerative diseases.
authors: Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Université Montpellier 2, Montpellier cedex 5, France.
authors: Sophie
authors: S
authors: Martin
authors: Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Université Montpellier 2, Montpellier cedex 5, France.
authors: Latifa
authors: L
authors: Zekri
authors: Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Université Montpellier 2, Montpellier cedex 5, France.
authors: Alexandra
authors: A
authors: Metz
authors: INSERM U 710, Université Montpellier 2, Montpellier cedex 5, France.
authors: Tangui
authors: T
authors: Maurice
authors: Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Université Montpellier 2, Montpellier cedex 5, France.
authors: Karim
authors: K
authors: Chebli
authors: Institut des biomolécules Max Mousseron UMR 5247, IBMM, Université Montpellier 2, Montpellier cedex 5, France.
authors: Michel
authors: M
authors: Vignes
authors: Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, Université Montpellier 2, Montpellier cedex 5, France.
authors: Jamal
authors: J
authors: Tazi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D002118:Calcium
keywords: G3BP; LTD; RNA; calcium homeostasis; short term synaptic plasticity; stress granules