Calcium is an important second messenger in the nervous system. One of the main mechanisms by which it transduces information within the cell is through the activation of calcium-dependent protein kinases such as the multifunctional calcium/calmodulin-dependent protein kinase II (CaMKII). CaMKII homologs have been found in all multicellular organisms that have been examined and have also been found in yeast. CaMKII from rat brain has been extensively studied, but many questions remain regarding its role in development, synaptic plasticity and higher functions such as learning and memory. Its localization to the post-synaptic density and its enzymatic properties suggest that this protein may be involved in formation of short-term memory or modulation of synaptic strength.

In Drosophila, we have shown that CaMKII is required for both behavioral plasticity in courtship learning and for normal synaptic function at the neuromuscular junction. CaMKII also has a role in development of the neuromuscular junction where it regulates the association of DLG, an adaptor protein that anchors adhesion molecules and ion channels, with the synapse.

The long-term goal of this research is to understand the signal transduction pathways underlying changes in synaptic structure and function. By starting with a protein kinase, we will be able to identify both upstream (receptors and other regulators of kinase level and activity) and downstream (substrates) elements of the pathway.

Selected Publications:

Temporal dynamics of neuronal activation by Channelrhodopsin-2 and TRPA1 determine behavioral output in Drosophila larvae. Pulver SR, Pashkovski SL, Hornstein NJ, Garrity PA, Griffith LC. J Neurophysiol. 2009 Jun;101(6):3075-88. [abstract]

Channelrhodopsin2 mediated stimulation of synaptic potentials at Drosophila neuromuscular junctions. Hornstein NJ, Pulver SR, Griffith LC. J Vis Exp. 2009 Mar 16;(25). [abstract]

High-resolution video tracking of locomotion in adult Drosophila melanogaster. Slawson JB, Kim EZ, Griffith LC. J Vis Exp. 2009 Feb 20;(24). [abstract]

Sun XX, Bostrom SL, Griffith LC. Alternative splicing of the eag potassium channel gene in Drosophila generates a novel signal transduction scaffolding protein. Mol Cell Neurosci. 2008. [abstract]

Shang Y, Griffith LC, Rosbash M. Light-arousal and circadian photoreception circuits intersect at the large PDF cells of the Drosophila brain. Proc Natl Acad Sci U S A. 2008;105(50):19587-94. [full text in PubMed Central] [abstract]

Parisky KM, Agosto J, Pulver SR, Shang Y, Kuklin E, Hodge JJ, et al. PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit. Neuron. 2008;60(4):672-82. [abstract]

Griffith LC, Rosbash M. Sleep: hitting the reset button. Nat Neurosci. 2008;11(2):123-4. [abstract]

Griffith LC. CaMKII: new tricks for an old dog. Cell. 2008;133(3):397-9. [abstract]

Griffith LC. Neuroscience - Love hangover. Nature. 2008;451(7174):24-5. [abstract]

Ejima A, Griffith LC. Courtship initiation is stimulated by acoustic signals in Drosophila melanogaster. PLoS ONE. 2008;3(9):e3246. [abstract]

Agosto J, Choi JC, Parisky KM, Stilwell G, Rosbash M, Griffith LC. Modulation of GABA(A) receptor desensitization uncouples sleep onset and maintenance in Drosophila. Nat Neurosci. 2008;11(3):354-9. [abstract]

Pulver SR, Griffith LC. Dr. Strangeslug, or how I learned to stop worrying and love the brain. Nat Neurosci. 2007;10(8):933. [abstract]

Mullasseril P, Dosemeci A, Lisman JE, Griffith LC. A structural mechanism for maintaining the 'on-state' of the CaMKII memory switch in the post-synaptic density. J Neurochem. 2007;103(1):357-64.[abstract]

Mattaliano MD, Montana ES, Parisky KM, Littleton JT, Griffith LC. The Drosophila ARC homolog regulates behavioral responses to starvation. Mol Cell Neurosci. 2007;36(2):211-21. [abstract]

Ejima A, Smith BP, Lucas C, van der Goes van Naters W, Miller CJ, Carlson JR, et al. Generalization of Courtship Learning in Drosophila Is Mediated by cis-Vaccenyl Acetate. Curr Biol. 2007;17(7):599-605. [abstract]

Griffith LC, Budnik V. (2006) Plasticity and second messengers during synapse development. Int Rev Neurobiol. 2006;75:237-65. Review.

Mehren JE, Griffith LC. (2006) Cholinergic neurons mediate CaMKII-dependent enhancement of courtship suppression. Learn Mem. 2006 Nov-Dec;13(6):686-9. Epub 2006 Nov 13. [abstract]

Hodge JJ, Mullasseril P, Griffith LC. Activity-dependent gating of CaMKII autonomous activity by Drosophila CASK. Neuron. 2006 Aug 3;51(3):327-37. [abstract]

Park D, Griffith LC. (2006) Electrophysiological and anatomical characterization of PDF-positive clock neurons in the intact adult Drosophila brain. J Neurophysiol. 2006 Jun;95(6):3955-60. Epub 2006 Mar 22. [abstract]

Slonimsky JD, Mattaliano MD, Moon JI, Griffith LC, Birren SJ. (2006) Role for calcium/calmodulin-dependent protein kinase II in the p75-mediated regulation of sympathetic cholinergic transmission. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2915-9. Epub 2006 Feb 13. [abstract]

Griffith LC. (2006) Watching the fly brain learn. Neuron. 2006 Jan 19;49(2):171-4. [abstract]

Ejima, A., Smith, B.P.C., Lucas, C., Levine, J.D. and Griffith, L.C. (2005) Sequential learning of pheromonal cues modulates memory consolidation in trainer-specific associative courtship conditioning. Curr Biol. 15:194-206. [abstract]

Hodge JJ, Choi JC, O'kane CJ, Griffith LC. (2004) Shaw potassium channel genes in Drosophila. J Neurobiol. 2005 Mar 4; [abstract]

Griffith LC. (2004) Receptor clustering: nothing succeeds like success. Curr Biol. 14(11):R413-5. [abstract]

Griffith, L.C. (2004) Calcium/calmodulin-dependent protein kinase II: An unforgettable kinase. J. Neurosci. 24:8391-8393.

Griffith, L.C. (2004) Regulation of calcium/calmodulin-dependent protein kinase II activation by intramolecular and intermolecular interactions. J. Neurosci. 24:8394-8398.

Mehren, J.E., Ejima, A. and Griffith, L.C. (2004) Unconventional sex: Fresh approaches to courtship learning. Curr. Opin. Neurobiol. 14:745-750 [abstract]

Mehren, J.E. and Griffith, L.C. (2004) Calcium-independent CaMKII in the adult Drosophila CNS enhances the training of pheromonal cues. J. Neurosci. 24:10584-10593.[abstract]

Sun XX, Hodge JJ, Zhou Y, Nguyen M, Griffith LC. (2004) "The eag potassium channel binds and locally activates calcium/calmodulin-dependent protein kinase II." J Biol Chem. 279(11):10206-14. [abstract]

Choi JC, Park D, Griffith LC. (2004) "Electrophysiological and morphological characterization of identified motor neurons in the Drosophila third instar larva central nervous system." J Neurophysiol. 91(5):2353-65. [abstract]

Pratt, K., Watt, A., Griffith, L.C., Nelson, S.B. and Turrigiano, G.G. (2003) "Activity-dependent remodeling of presynaptic inputs by postsynaptic expression of activated CaMKII" Neuron 39:269-281. [abstract]

Griffith, L.C., Lu, C.S. and Sun, X.X. (2003) "CaMKII, an Enzyme on the Move: Regulation of Temporospatial Localization" Mol. Interv. 3:386-403

Lu, C., Hodge, J.J.L., Sun, X.-X., Mehren, J.E. and Griffith, L.C. (2003) "Regulation of the Ca2+/CaM responsive pool of CaMKII by scaffold-dependent autophosphorylation" Neuron, 40(6):1185-97.[abstract]

Park, D., Coleman, M.J., Budnik, V. and Griffith, L.C. (2002) "Regulation of neuronal excitability in Drosophila by constitutively active CaMKII " J. Neurobiol. 52:24-42. [abstract]

Wang, Z., Wilson, G.F. and Griffith, L.C. (2002) "Calcium/calmodulin-dependent protein kinase II phosphorylates and regulates the Drosophila Eag potassium channel" J. Biol. Chem. 227:24022-24029. [abstract]

Griffith LC. (2001) Potassium channels: the importance of transport signals. Curr Biol. 11:R226-8. [abstract]

Joiner MA, Griffith LC. (2000). Visual input regulates circuit configuration in courtship conditioning of Drosophila melanogaster. Learn Mem. 7:32-42. [abstract]

Long X, Griffith LC. (2000) Identification and characterization of a SUMO-1 conjugation system that modifies neuronal Calcium/Calmodulin-dependent protein kinase II in drosophila melanogaster. J Biol Chem. 275:40765-76. [abstract]

GuptaRoy B, Marwaha N, Pla M, Wang Z, Nelson HB, Beckingham K, Griffith LC. (2000) Alternative splicing of Drosophila calcium/calmodulin-dependent protein kinase II regulates substrate specificity and activation. Brain Res Mol Brain Res. 80:26-34. [abstract]

Joiner MA, Griffith LC. (1999). Mapping of the anatomical circuit of CaM kinase-dependent courtship conditioning in Drosophila. Learn. Mem. 6:177-92. [abstract]

Koh YH, Popova E, Thomas U, Griffith LC, Budnik V. (1999). Regulation of DLG localization at synapses by CaMKII-dependent phosphorylation. Cell 98:353-363. [abstract]

Wang, Z., Palmer, G., and Griffith, L.C. (1998). Regulation of Drosophila Ca²⁺/calmodulin-dependent protein kinase II by autophosphorylation analyzed by site-directed mutagenesis. J. Neurochem. 71:378-387. [abstract]

Otmakhov, N., Griffith, L.C., and Lisman, J.E. 1997. Postsynaptic inhibitors of Calcium/Calmodulin-dependent protein kinase type II block induction but not maintenance of pairing-induced long-term potentiation. J. Neurosci. 17:5357-5365. [abstract] [full text]

Barria, A., Muller, D., Derkach, V., Griffith, L.C., and Soderling, T.R. 1997. Regulatory Phosphorylation of AMPA-Type Glutamate Receptors by CaM-KII During Long-Term Potentiation. Science 276:2042-2045. [abstract]

Joiner, M.A. and Griffith, L.C. 1997. CaM Kinase II and Visual Input Modulate Memory Formation in the Neuronal Circuit Controlling Courtship Conditioning J. Neurosci. 17: 9384-9391. [abstract] [full text]

GuptaRoy, B. and Griffith, L.C. 1996. Functional characterization of alternatively spliced isoforms of Drosophila Ca²⁺/calmodulin-dependent protein kinase II. J. Neurochem. 66:1282-1288. [abstract]

GuptaRoy, B., Beckingham, K. and Griffith, L.C. 1996. Functional diversity of alternatively spliced isoforms of Drosophila Ca²⁺/calmodulin-dependent protein kinase II: A role for the variable domain in activation J. Biol. Chem. 271:19846-19851. [abstract]

Griffith, L.C., Wang, J., Zhong, Y., Wu, C.-F. and Greenspan, R.J. 1994. Interaction between CaM kinase II and potassium channel subunit Eag affects plasticity in Drosophila. Proc. Natl. Acad. Sci. USA, 91: 10044-10048. [abstract]

Wang, J., Renger, J., Griffith, L.C., Greenspan, R.J. and Wu, C.-F. 1994. Concomitant Alterations of Physiological and Developmental Plasticity at CaM kinase II-inhibited Synapses in Drosophila. Neuron 13: 1373-1384. [abstract]

Griffith, L.C., Verselis, L.M., Aitken, K.M., Kyriacou, C.P., Danho, W. and Greenspan, R.J. 1993. Inhibition of calcium/calmodulin-dependent protein kinase in Drosophila disrupts behavioral plasticity. Neuron 10: 501-509. [abstract]

Griffith, L.C. and Greenspan, R.J. 1993. The diversity of calcium/calmodulin-dependent protein kinase II isoforms in Drosophila is generated by alternative splicing of a single gene. J. Neurochem 61: 1534-1537. [abstract]

 

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