CaMKII plays an important role in learning in Drosophila as well as in other animals. Localization of CaMKII allows this highly abundant enzyme to achieve specificity of action. Scaffolding interactions can also regulate the activity of CaMKII. We have characterized two such interactions: an interaction with the Eag potassium channel that renders the enzyme constitutively active without kinase autophosphorylation and an ATP-dependent interaction with Camguk (Cmg), a MAGUK protein that enhances inactivating autophosphorylation of the kinase.
Our specific aims are: 1) Determine the role of alternative splicing in the subcellular localization of CaMKII. CaMKII localization is aberrant in a mutant that alters CaMKII isoform ratios and CaMKII can enter the nucleus in eag mutants. We will investigate the mechanisms of CaMKII subcellular localization and nuclear translocation. 2) Determine the role of the CaMKIhEag complex. We will define the molecular basis of the interaction and use this information to design specific inhibitors to use in vivo in electrophysiological and behavioral assays. 3) Determine the role of the CaMKIhCmg complex. We will define the molecular basis of the interaction and use inhibitors and overexpression to probe the role of Cmg in the regulation of CaMKII activity. Cmg promotes formation of a calcium-insensitive pool of CaMKII which may be important in modulating calcium signaling during plasticity. These studies will provide insight into the regulation of a protein that is fundamental to synaptic plasticity. Understanding these pathways will advance our knowledge of the basic processes that shape behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM054408-11S1
Application #
7363290
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (01))
Program Officer
Tompkins, Laurie
Project Start
1996-05-01
Project End
2007-08-31
Budget Start
2006-05-01
Budget End
2007-08-31
Support Year
11
Fiscal Year
2007
Total Cost
$101,508
Indirect Cost
Name
Brandeis University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Kuklin, Elena A; Alkins, Stephen; Bakthavachalu, Baskar et al. (2017) The Long 3'UTR mRNA of CaMKII Is Essential for Translation-Dependent Plasticity of Spontaneous Release in Drosophila melanogaster. J Neurosci 37:10554-10566
Langenhan, Tobias; Barr, Maureen M; Bruchas, Michael R et al. (2015) Model Organisms in G Protein-Coupled Receptor Research. Mol Pharmacol 88:596-603
Slawson, Justin B; Kuklin, Elena A; Mukherjee, Konark et al. (2014) Regulation of dopamine release by CASK-? modulates locomotor initiation in Drosophila melanogaster. Front Behav Neurosci 8:394
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Trott, Alexander R; Donelson, Nathan C; Griffith, Leslie C et al. (2012) Song choice is modulated by female movement in Drosophila males. PLoS One 7:e46025
Maiya, Rajani; Lee, Seonok; Berger, Karen H et al. (2012) DlgS97/SAP97, a neuronal isoform of discs large, regulates ethanol tolerance. PLoS One 7:e48967
Donelson, Nathan C; Donelson, Nathan; Kim, Eugene Z et al. (2012) High-resolution positional tracking for long-term analysis of Drosophila sleep and locomotion using the ""tracker"" program. PLoS One 7:e37250

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