Calpain activity contributes to the control of SNAP-25 levels in neurons

Calpains are a family of calcium-dependent proteases with abundant expression in the CNS, and potent in cleaving some synaptic components. Assessment of calpain activity by its fluorescent substrate, Boc-Leu-Met-CMAC, revealed that cultured neurons display a significant level of constitutive enzyme...

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Published in:Molecular and cellular neuroscience 2008-10, Vol.39 (3), p.314-323
Main Authors: Grumelli, Carlotta, Berghuis, Paul, Pozzi, Davide, Caleo, Matteo, Antonucci, Flavia, Bonanno, Giambattista, Carmignoto, Giorgio, Dobszay, Marton Benedek, Harkany, Tibor, Matteoli, Michela, Verderio, Claudia
Format: Article
Language:English
Subjects:
Animals
Brain-Derived Neurotrophic Factor - metabolism
Calcium - metabolism
Calpain - metabolism
Cells, Cultured
Coumarins - chemistry
Coumarins - metabolism
Dipeptides - metabolism
Embryo, Mammalian - anatomy & histology
Excitatory Amino Acid Agonists - pharmacology
gamma-Aminobutyric Acid - metabolism
Glutamic Acid - metabolism
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - metabolism
Kainic Acid - pharmacology
Mice
Mice, Inbred C57BL
Neurons - cytology
Neurons - metabolism
Patch-Clamp Techniques
Protein Isoforms - genetics
Protein Isoforms - metabolism
Rats
Seizures - chemically induced
Seizures - metabolism
Synaptosomal-Associated Protein 25 - genetics
Synaptosomal-Associated Protein 25 - metabolism
Synaptosomes - metabolism
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Summary:Calpains are a family of calcium-dependent proteases with abundant expression in the CNS, and potent in cleaving some synaptic components. Assessment of calpain activity by its fluorescent substrate, Boc-Leu-Met-CMAC, revealed that cultured neurons display a significant level of constitutive enzyme activity. Notably, calpain activity differs in distinct neuronal populations, with a significantly higher level of activity in GABAergic cells. Using selectively-enriched cultures of fast-spiking GABAergic interneurons, we show that calpain activity partially contributes to the post-translational down regulation of SNAP-25, a calpain substrate, in differentiated GABA cells. In addition, we demonstrate that SNAP-25 is cleaved by calpain in response to acute seizures induced by intraperitoneal kainate injection in vivo. These data indicate that calpains in neurons are active even at physiological calcium concentrations and that different levels of calpain activation in selected neuron subtypes may contribute to the pattern of synaptic protein expression.
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2008.07.011