While learning and memory have mystified people for centuries, a cellular model for these processes eluded scientists until the discovery of LTP and LTD in the 1970s. Three decades later a general biochemical cascade involving calcium/calmodulin-dependent kinase II (CaMKII), protein phosphatase 1 (PP-1), and inhibitor-1 has gained widespread acceptance, although many details remain obscure. This proposal will employ biochemical and neuropharmacological techniques to characterize a novel phosphorylation event on inhibitor-1 by cyclin-dependent kinase 5 (Cdk5) and its implications for synaptic plasticity. The kinetics of this phosphorylation reaction and its effect upon inhibitor-1 activation, deactivation, and inhibitory activity against PP-1 will be assessed. Hippocampal slices will then be used to characterize this event in vivo, in terms of basal levels of phosphorylation, as well as modulation by different signaling pathways and possible effects on downstream PP-1 targets. Finally, the phosphatase(s) responsible for dephosphorylation of this site will be determined by both in vitro and in vivo methods.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30MH072062-01A1
Application #
6938801
Study Section
Special Emphasis Panel (ZRG1-F03B (20))
Program Officer
Curvey, Mary F
Project Start
2005-06-01
Project End
2008-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
1
Fiscal Year
2005
Total Cost
$30,712
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Genetics
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Nguyen, Chan; Hosokawa, Tomohisa; Kuroiwa, Mahomi et al. (2007) Differential regulation of the Cdk5-dependent phosphorylation sites of inhibitor-1 and DARPP-32 by depolarization. J Neurochem 103:1582-93
Nguyen, Chan; Nishi, Akinori; Kansy, Janice W et al. (2007) Regulation of protein phosphatase inhibitor-1 by cyclin-dependent kinase 5. J Biol Chem 282:16511-20