Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 326 (5956): 1127-1130

Copyright © 2009 by the American Association for the Advancement of Science

The Schizophrenia Susceptibility Gene dysbindin Controls Synaptic Homeostasis

Dion K. Dickman, and Graeme W. Davis*

Abstract: The molecular mechanisms that achieve homeostatic stabilization of neural function remain largely unknown. To better understand how neural function is stabilized during development and throughout life, we used an electrophysiology-based forward genetic screen and assessed the function of more than 250 neuronally expressed genes for a role in the homeostatic modulation of synaptic transmission in Drosophila. This screen ruled out the involvement of numerous synaptic proteins and identified a critical function for dysbindin, a gene linked to schizophrenia in humans. We found that dysbindin is required presynaptically for the retrograde, homeostatic modulation of neurotransmission, and functions in a dose-dependent manner downstream or independently of calcium influx. Thus, dysbindin is essential for adaptive neural plasticity and may link altered homeostatic signaling with a complex neurological disease.

Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.

* To whom correspondence should be addressed. E-mail: graeme.davis{at}ucsf.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
RIM Controls Homeostatic Plasticity through Modulation of the Readily-Releasable Vesicle Pool.
M. Muller, K. S. Y. Liu, S. J. Sigrist, and G. W. Davis (2012)
J. Neurosci. 32, 16574-16585
   Abstract »    Full Text »    PDF »
Snapin is Critical for Presynaptic Homeostatic Plasticity.
D. K. Dickman, A. Tong, and G. W. Davis (2012)
J. Neurosci. 32, 8716-8724
   Abstract »    Full Text »    PDF »
Spontaneous transmitter release is critical for the induction of long-term and intermediate-term facilitation in Aplysia.
I. Jin, S. Puthanveettil, H. Udo, K. Karl, E. R. Kandel, and R. D. Hawkins (2012)
PNAS 109, 9131-9136
   Abstract »    Full Text »    PDF »
Lola regulates glutamate receptor expression at the Drosophila neuromuscular junction.
A. Fukui, M. Inaki, G. Tonoe, H. Hamatani, M. Homma, T. Morimoto, H. Aburatani, and A. Nose (2012)
Biology Open 1, 362-375
   Abstract »    Full Text »    PDF »
Quantitative Proteomic and Genetic Analyses of the Schizophrenia Susceptibility Factor Dysbindin Identify Novel Roles of the Biogenesis of Lysosome-Related Organelles Complex 1.
A. Gokhale, J. Larimore, E. Werner, L. So, A. Moreno-De-Luca, C. Lese-Martin, V. V. Lupashin, Y. Smith, and V. Faundez (2012)
J. Neurosci. 32, 3697-3711
   Abstract »    Full Text »    PDF »
The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse.
J. Larimore, K. Tornieri, P. V. Ryder, A. Gokhale, S. A. Zlatic, B. Craige, J. D. Lee, K. Talbot, J.-F. Pare, Y. Smith, et al. (2011)
Mol. Biol. Cell 22, 4854-4867
   Abstract »    Full Text »    PDF »
Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila.
L. Shao, Y. Shuai, J. Wang, S. Feng, B. Lu, Z. Li, Y. Zhao, L. Wang, and Y. Zhong (2011)
PNAS 108, 18831-18836
   Abstract »    Full Text »    PDF »
S6 kinase localizes to the presynaptic active zone and functions with PDK1 to control synapse development.
L. Cheng, C. Locke, and G. W. Davis (2011)
J. Cell Biol. 194, 921-935
   Abstract »    Full Text »    PDF »
Rapid Active Zone Remodeling during Synaptic Plasticity.
A. Weyhersmuller, S. Hallermann, N. Wagner, and J. Eilers (2011)
J. Neurosci. 31, 6041-6052
   Abstract »    Full Text »    PDF »
The RhoGAP crossveinless-c Interacts with Dystrophin and Is Required for Synaptic Homeostasis at the Drosophila Neuromuscular Junction.
G. S. K. Pilgram, S. Potikanond, M. C. van der Plas, L. G. Fradkin, and J. N. Noordermeer (2011)
J. Neurosci. 31, 492-500
   Abstract »    Full Text »    PDF »
Nucleocytoplasmic Shuttling of Dysbindin-1, a Schizophrenia-related Protein, Regulates Synapsin I Expression.
E. Fei, X. Ma, C. Zhu, T. Xue, J. Yan, Y. Xu, J. Zhou, and G. Wang (2010)
J. Biol. Chem. 285, 38630-38640
   Abstract »    Full Text »    PDF »
Reduced Survival of Motor Neuron (SMN) Protein in Motor Neuronal Progenitors Functions Cell Autonomously to Cause Spinal Muscular Atrophy in Model Mice Expressing the Human Centromeric (SMN2) Gene.
G.-H. Park, Y. Maeno-Hikichi, T. Awano, L. T. Landmesser, and U. R. Monani (2010)
J. Neurosci. 30, 12005-12019
   Abstract »    Full Text »    PDF »
Compensation for Variable Intrinsic Neuronal Excitability by Circuit-Synaptic Interactions.
R. Grashow, T. Brookings, and E. Marder (2010)
J. Neurosci. 30, 9145-9156
   Abstract »    Full Text »    PDF »
Successful Learning in Schizophrenia, Functional Neuroimaging Studies, and Theoretical Considerations.
H. H. Holcomb and G. K. Murray (2010)
Schizophr Bull 36, 463-464
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882