Calpain product of WT-CRMP2 reduces the amount of surface NR2B NMDA receptor subunit.
The brain is particularly vulnerable to ischaemia; however, neurons can become tolerant to ischaemic insult. This tolerance has been shown to involve activation of NMDA receptors, but its mechanisms have not yet been fully elucidated. Using a preconditioning protocol, we show that neurons surviving to a transient NMDA exposure become resistant to the glutamatergic agonist. Using a proteomic approach, we found that alterations of the protein pattern of NMDA-resistant neurons are restricted mainly to the five collapsin response mediator proteins (CRMPs). A sustained increase in calpain activity following NMDA treatment is responsible for the production of cleaved CRMPs. Finally, we provide evidence for the involvement of the cleaved form of WT-CRMP2 in the down-regulation of NR2B. Our data suggests that, beside their role in neuronal morphogenesis, CRMPs may contribute to neuronal plasticity.
Bretin
Sylvie
S
INSERM, Collège de France, Paris, France.
Rogemond
Véronique
V
Marin
Philippe
P
Maus
Marion
M
Torrens
Yvette
Y
Honnorat
Jérôme
J
Glowinski
Jacques
J
Prémont
Joël
J
Gauchy
Christian
C
D000818:Animals; D001710:Biotin / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000096:biosynthesis / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D018690:Excitatory Amino Acid Agonists; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; C095114:collapsin response mediator protein-2; D018698:Glutamic Acid; D016202:N-Methylaspartate; D001710:Biotin; D002154:Calpain; D002118:Calcium