title: The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function.
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.
authors.affiliation: Pfizer Neuroscience Research Unit, Princeton, NJ, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: E I
authors.initials: EI
authors.lastname: Charych
authors.forename: V L
authors.initials: VL
authors.lastname: Pulito
authors.forename: J B
authors.initials: JB
authors.lastname: Lee
authors.forename: N M
authors.initials: NM
authors.lastname: Graziane
authors.forename: R A
authors.initials: RA
authors.lastname: Crozier
authors.forename: R
authors.initials: R
authors.lastname: Revilla-Sanchez
authors.forename: M P
authors.initials: MP
authors.lastname: Kelly
authors.forename: A J
authors.initials: AJ
authors.lastname: Dunlop
authors.forename: H
authors.initials: H
authors.lastname: Murdoch
authors.forename: N
authors.initials: N
authors.lastname: Taylor
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.forename: M
authors.initials: M
authors.lastname: Pausch
authors.forename: A
authors.initials: A
authors.lastname: Hayashi-Takagi
authors.forename: K
authors.initials: K
authors.lastname: Ishizuka
authors.forename: S
authors.initials: S
authors.lastname: Seshadri
authors.forename: B
authors.initials: B
authors.lastname: Bates
authors.forename: K
authors.initials: K
authors.lastname: Kariya
authors.forename: A
authors.initials: A
authors.lastname: Sawa
authors.forename: R J
authors.initials: RJ
authors.lastname: Weinberg
authors.forename: S J
authors.initials: SJ
authors.lastname: Moss
authors.forename: M D
authors.initials: MD
authors.lastname: Houslay
authors.forename: Z
authors.initials: Z
authors.lastname: Yan
authors.forename: N J
authors.initials: NJ
authors.lastname: Brandon
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D057907:Post-Synaptic Density / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000378:metabolism*
chemical_list: C498794:Disc1 protein, mouse; C498795:Disc1 protein, rat; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; C545105:TNIK protein, mouse; C553969:TNIK protein, rat