Memory and Learning: Cdk5 tells a tail to remember

Abstract

Scientists have added to the list of proteins that might regulate learning and memory. New work hints that Cdk5--a protein with numerous other functions in the brain--also helps a class of glutamate receptors known as N -methyl-D-aspartate (NMDA) receptors function properly as they facilitate learning. Li and colleagues report that Cdk5, a member of the cyclin-dependent kinase family of proteins (which have achieved fame for coordinating the cell cycle), is located near NMDA receptors at synapses. With fluorescent labels that distinguish Cdk5 and the NMDA receptor, the team visualized these proteins in cultured neurons and found that the patterns overlapped. This result suggests that Cdk5 and the NMDA receptor physically associate with each other. To test this idea, the researchers used antibodies to grab Cdk5 from brain extracts. This procedure captured the receptor in addition to Cdk5, indicating that the two bind to each other. The researchers next applied a chemical inhibitor of Cdk5 to slices of hippocampus, the memory center of the brain. This treatment decreases the flow of electrical current through the receptor and blocks long-term potentiation: the persistent strengthening of neuronal signals that many believe is the initial step in making new memories. Other results hint at a possible mechanism: In vitro, Cdk5 can chemically modify the long tail of an NMDA receptor subunit. Although this work is preliminary, it provides an impetus to figure out whether Cdk5 chemically alters NMDA receptors in vivo and whether the modifications alter receptor function. --R. John Davenport (At deadline time, full hyperlink and reference information was not yet available.) B.-S. Li, H. C. Pant, M.-K. Sun, L. Zhang, S. Takahashi, A. B. Kulkarni, W. Ma, L. Vinade, R. O. Brady, Regulation of NMDA receptors by cyclin-dependent kinase-5. PNAS Early Edition 2 (issue no. 40) (2001). [Full Text]