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:
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]
View Complete Publication List on PubMed:
Leslie Griffith
Last reviewed: Feb. 15, 2007. E-mail comments
or questions to the webmaster.
