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

Q. Wang, E. I. Charych, V. L. Pulito, J. B. Lee, N. M. Graziane, R. A. Crozier, R. Revilla-Sanchez, M. P. Kelly, A. J. Dunlop, H. Murdoch, N. Taylor, Y. Xie, M. Pausch, A. Hayashi-Takagi, Koko Ishizuka, S. Seshadri, B. Bates, K. Kariya, Akira Sawa, R. J. WeinbergS. J. Moss, M. D. Houslay, Z. Yan, N. J. Brandon

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1006-1023
Number of pages18
JournalMolecular Psychiatry
Volume16
Issue number10
DOIs
Publication statusPublished - Oct 2011

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Keywords

  • DISC1
  • schizophrenia
  • synapse
  • TNIK

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Wang, Q., Charych, E. I., Pulito, V. L., Lee, J. B., Graziane, N. M., Crozier, R. A., ... Brandon, N. J. (2011). The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. Molecular Psychiatry, 16(10), 1006-1023. https://doi.org/10.1038/mp.2010.87