The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function

Wang, Q. et al. (2011) The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. Molecular Psychiatry, 16(10), pp. 1006-1023. (doi: 10.1038/mp.2010.87)

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Publisher's URL: http://dx.doi.org/10.1038/mp.2010.87

Abstract

Disrupted in schizophrenia 1 (DISC1), a genetic risk factor for multiple serious psychiatric diseases including schizophrenia, bipolar disorder and autism, is a key regulator of multiple neuronal functions linked to both normal development and disease processes. As these diseases are thought to share a common deficit in synaptic function and architecture, we have analyzed the role of DISC1 using an approach that focuses on understanding the protein–protein interactions of DISC1 specifically at synapses. We identify the Traf2 and Nck-interacting kinase (TNIK), an emerging risk factor itself for disease, as a key synaptic partner for DISC1, and provide evidence that the DISC1–TNIK interaction regulates synaptic composition and activity by stabilizing the levels of key postsynaptic density proteins. Understanding the novel DISC1–TNIK interaction is likely to provide insights into the etiology and underlying synaptic deficits found in major psychiatric diseases.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Houslay, Professor Miles
Authors: Wang, Q., Charych, E. I., Pulito, V. L., Lee, J. B., Graziane, N. M., Crozier, R. A., Revilla-Sanchez, R., Kelly, M. P., Dunlop, A. J., Murdoch, H., Taylor, N., Xie, Y., Pausch, M., Hayashi-Takagi, A., Ishizuka, K., Seshadri, S., Bates, B., Kariya, K., Sawa, A., Weinberg, R. J., Moss, S. J., Houslay, M.D., Yan, Z., and Brandon, N. J.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Molecular Psychiatry
Publisher:Nature Publishing Group
ISSN:1359-4184
ISSN (Online):1476-5578
Published Online:14 September 2010
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438301Phosphodiesterase-4 isoforms - intracellular targeting, regulation and potential therapeutic targetsMiles HouslayMedical Research Council (MRC)G0600765Institute of Neuroscience and Psychology