Brain-Derived Neurotrophic Factor and Epidermal Growth Factor Activate Neuronal m-Calpain via Mitogen-Activated Protein Kinase-Dependent Phosphorylation

• DOI: 10.1523/jneurosci.5120-09.2010
• Publication Date: 2010-01-20T20:23:27Z
• Authors: Sohila Zadran; Hussam Jourdi; Karoline Rostamiani; Qingyu Qin; Xiaoning Bi; Michel Baudry
• Keywords: Calpastatin; Cyclin-dependent kinase 5

Calpain is a calcium-dependent protease that plays significant role in synaptic plasticity, cell motility, and neurodegeneration. Two major calpain isoforms are present brain, with μ-calpain (calpain1) requiring micromolar calcium concentrations for activation m-calpain (calpain2) needing millimolar concentrations. Recent studies fibroblasts indicate epidermal growth factor (EGF) can activate independently of via mitogen-activated protein kinase (MAPK)-mediated phosphorylation. In neurons, MAPK activated by both brain-derived neurotrophic (BDNF) EGF. We therefore examined whether these factors could MAPK-dependent phosphorylation using cultured primary neurons HEK–TrkB cells, which express BDNF EGF receptors. was monitored quantitative analysis spectrin degradation fluorescence resonance energy transfer (FRET)-based assay, assessed the truncation calpain-specific peptide flanked FRET fluorophore pair DABCYL EDANS. types, rapidly elicited activation, completely blocked inhibitors. stimulated but not serine phosphorylation, an effect also Remarkably, BDNF- EGF-induced preferentially localized dendrites dendritic spines hippocampal associated actin polymerization, prevented inhibition. Our results that, MAPK-mediated These strongly support plasticity may explain why m-calpain, although widely expressed CNS, requires nonphysiological levels activation.