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Biotech / Medical : Indications -- Stroke -- Ignore unavailable to you. Want to Upgrade?

To: keokalani'nui who wrote (7)	10/23/2001 9:33:11 PM
From: Miljenko Zuanic	Respond to of 70

Maybe something new in NMDA regulation. Published online before print October 2, 2001, 10.1073/pnas.211428098; Proc. Natl. Acad. Sci. USA, Vol. 98, Issue 22, 12742-12747, October 23, 2001 From the Cover Neurobiology Regulation of NMDA receptors by cyclin-dependent kinase-5 Bing-Sheng Li, Miao-Kun Sun, Lei Zhang, Satoru Takahashi§, Wu Ma¶, Lucia Vinade, Ashok B. Kulkarni§, Roscoe O. Brady, and Harish C. Pant, * Laboratory of Neurochemistry, Laboratory of Adaptive Systems, and Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; Behavioral Endocrinology Branch, National Institute of Mental Health, and § Functional Genomics Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892; ¶ Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington, D.C. 20375; and ** Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 Contributed by Roscoe O. Brady, August 14, 2001 Members of the N-methyl-D-aspartate (NMDA) class of glutamate receptors (NMDARs) are critical for development, synaptic transmission, learning and memory; they are targets of pathological disorders in the central nervous system. NMDARs are phosphorylated by both serine/threonine and tyrosine kinases. Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.