Survival response-linked Pyk2 activation during potassium depletion-induced apoptosis of cerebellar granule neurons

Autor: Béatrice Blot, Flavie Strappazzon, Rémy Sadoul, Sakina Torch, Yaël Trioulier, Jean Marc Verna
Přispěvatelé: Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), This study was partly supported by the Institut National de la Santé et de la Recherche Médicale, the University Joseph Fourier and by funds from the Association Française contre les Myopathies and Région Rhône-Alpes. Flavie Strappazzon is the recipient of a grant from the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche., Fraboulet, Sandrine, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Rok vydání: 2007
Předmět:
Cerebellar granule neurons
Time Factors
MESH: Drug Interactions
MESH: Neurons
Tetrazolium Salts
Apoptosis
MESH: Chelating Agents
MESH: Animals
Newborn
MESH: Tyrosine
MESH: Dose-Response Relationship
Drug
Potassium Chloride
Mice
0302 clinical medicine
Cerebellum
Serine
MESH: Animals
Drug Interactions
Egtazic Acid
MESH: Mutagenesis
Chelating Agents
Neurons
0303 health sciences
biology
Autophosphorylation
Depolarization
MESH: Tetrazolium Salts
Cell biology
MESH: Cell Survival
Caspases
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Signal transduction
MESH: Focal Adhesion Kinase 2
Intracellular
Potassium depletion
MESH: Enzyme Activation
Calmodulin
MESH: Egtazic Acid
Cell Survival
MESH: Thiazoles
Transfection
03 medical and health sciences
Cellular and Molecular Neuroscience
MESH: Analysis of Variance
Ca2+/calmodulin-dependent protein kinase
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Extracellular
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
MESH: Serine
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
MESH: Mice
Molecular Biology
Membrane depolarization
030304 developmental biology
Pyk2
Analysis of Variance
MESH: Caspases
Dose-Response Relationship
Drug
MESH: Transfection
MESH: Apoptosis
MESH: Time Factors
Cell Biology
MESH: Cerebellum
Enzyme Activation
Thiazoles
Focal Adhesion Kinase 2
Animals
Newborn
Mutagenesis
MESH: Potassium Chloride
MESH: Potassium
Potassium
biology.protein
Tyrosine
030217 neurology & neurosurgery
Zdroj: Molecular and Cellular Neuroscience
Molecular and Cellular Neuroscience, Elsevier, 2007, 34 (3), pp.355-65. ⟨10.1016/j.mcn.2006.11.012⟩
Molecular and Cellular Neuroscience, 2007, 34 (3), pp.355-65. ⟨10.1016/j.mcn.2006.11.012⟩
ISSN: 1044-7431
1095-9327
DOI: 10.1016/j.mcn.2006.11.012
Popis: International audience; Numerous extracellular stimuli trigger trans-autophosphorylation at Tyr402 of Pyk2, inducing its activation. Pyk2 is a key mediator of several signaling pathways and has been implicated in apoptosis induced by specific stress signals. We investigated whether Pyk2 participates in cerebellar granule neuron (CGN) apoptosis induced by the suppression of membrane depolarization. We demonstrate that shifting CGN cultures from 25 mM to 5 mM KCl-containing medium induces an early, transient 70% increase in phosphorylated Tyr402 and Tyr580 Pyk2 levels that is triggered by Ca(2+) released from intracellular stores and mediated by calmodulin (CaM). Overexpression of Pyk2 increases CGN survival after 24 h by 70% compared to the control, thus suggesting that Pyk2 is involved in an anti-apoptotic response to K+ lowering. Furthermore, we show that CGN grown in K25 medium exhibit detectable CaM-dependent Pyk2 activity. When silencing Pyk2 activity by expressing a dominant-negative form, only 40% of the transfected neurons were alive 24 h after transfection when compared to the control. Overall, the present findings demonstrate for the first time that Pyk2 is a critical mediator of CGN survival.
Databáze: OpenAIRE
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