Both N-methyl-D-aspartate (NMDA) and non-NMDA receptors mediate glutamate-induced cleavage of the cyclin-dependent kinase 5 (cdk5) activator p35 in cultured rat hippocampal neurons.

Neuroscience Letters
Petri KerokoskiTuula Pirttilä

Abstract

Cyclin-dependent kinase 5 (cdk5) regulates crucial neurobiological events, and deregulation of cdk5 has been implicated in several neurodegenerative disorders. The deregulation is suggested to occur due to cleavage of the cdk5 activator protein p35 to a smaller p25 fragment by the calcium-activated protease calpain. Here we have elucidated the role of different calcium-permeable ionotropic glutamate receptors in the induction of p35 cleavage in cultured rat hippocampal neurons. The glutamate receptor agonists glutamic acid, N-methyl-D-aspartate (NMDA), kainic acid, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were all able to induce p35 cleavage, in a manner depending on extracellular calcium. The effect of glutamate was mediated by NMDA receptors, as it was prevented by the NMDA antagonist MK-801. Cyclothiazide (CTZ), an inhibitor of AMPA receptor desensitization, enhanced glutamate-induced p35 cleavage. In immature 6-day-old cultures the non-NMDA agonist kainic acid provoked p35 cleavage, whereas glutamate and NMDA were ineffective. The data suggest that both NMDA and non-NMDA receptors are able to induce p35 cleavage. Different factors, such as maturation state of neurons or desensitization properties ...Continue Reading

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Citations

Jan 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·Hee Jung ChungLily Yeh Jan
Aug 24, 2010·Journal of Ethnopharmacology·Jie ZhouJuan Chen
Jan 15, 2008·European Journal of Pharmacology·Bogachan SahinJames A Bibb
Sep 22, 2006·Journal of Neurochemistry·Ying-Peng WangGong Ju
Oct 13, 2006·Journal of Neurochemistry·Marco AngeloK Peter Giese
Nov 1, 2007·Journal of Neurochemistry·Mannie M Y FanLynn A Raymond
Jul 20, 2010·Bipolar Disorders·Natalia Crespo-BielMercè Pallàs
May 9, 2006·Biochemical and Biophysical Research Communications·Anne JämsäMervi Vasänge
Apr 14, 2015·Journal of Neurochemistry·Rafael Andres Posada-DuqueGloria Patricia Cardona-Gomez
Sep 17, 2014·Frontiers in Aging Neuroscience·John F Castro-AlvarezGloria P Cardona-Gómez
Dec 12, 2017·Frontiers in Cellular Neuroscience·Soledad FerrerasMaría G Paglini
Apr 3, 2007·The Journal of Biological Chemistry·Chan NguyenJames A Bibb
Jan 18, 2006·Journal of Neuropathology and Experimental Neurology·Arjune SenSanjay M Sisodiya
Aug 18, 2020·Journal of Alzheimer's Disease : JAD·Tam T QuachRuth M Barrientos
Feb 6, 2017·Neurochemical Research·Peter Frederikse, Chinnaswamy Kasinathan
Sep 13, 2012·Neuroreport·Masahiro NakamoriMasayasu Matsumoto
Oct 6, 2020·Journal of Alzheimer's Disease : JAD·Rafael Andrés Posada-Duque, Gloria Patricia Cardona-Gómez

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