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:
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.
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]
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.
Griffith LC, Rosbash M. Sleep: hitting the reset button. Nat Neurosci. 2008;11(2):123-4.
Griffith LC. CaMKII: new tricks for an old dog. Cell. 2008;133(3):397-9.
Griffith LC. Neuroscience - Love hangover. Nature. 2008;451(7174):24-5.
Ejima A, Griffith LC. Courtship initiation is stimulated by acoustic signals in Drosophila melanogaster. PLoS ONE. 2008;3(9):e3246.
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.
Pulver SR, Griffith LC. Dr. Strangeslug, or how I learned to stop worrying and love the brain. Nat Neurosci. 2007;10(8):933.
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.
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.
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.
Slonimsky JD, Mattaliano MD, Moon JI, Griffith LC, Birren SJ. 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.
Park D, Griffith LC. Electrophysiological and Anatomical Characterization of PDF-positive Clock Neurons in the Intact Adult Drosophila Brain. J Neurophysiol. 2006.
Mehren JE, Griffith LC. Cholinergic neurons mediate CaMKII-dependent enhancement of courtship suppression. Learn Mem. 2006;13(6):686-9.
Hodge JJ, Mullasseril P, Griffith LC. Activity-dependent gating of CaMKII autonomous activity by Drosophila CASK. Neuron. 2006;51(3):327-37.
Griffith LC, Budnik V. Plasticity and second messengers during synapse development. Int Rev Neurobiol. 2006;75:237-65.
Griffith LC. Watching the fly brain learn. Neuron. 2006;49(2):171-4.
Ejima A, Smith BP, Lucas C, Levine JD, Griffith LC. Sequential learning of pheromonal cues modulates memory consolidation in trainer-specific associative courtship conditioning. Curr Biol. 2005;15(3):194-206.
View Complete Publication List on PubMed:
Leslie Griffith
Last reviewed: Feb. 5, 2009. E-mail comments
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