The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function.
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.
Wang
Q
Q
Pfizer Neuroscience Research Unit, Princeton, NJ, USA.
Charych
E I
EI
Pulito
V L
VL
Lee
J B
JB
Graziane
N M
NM
Crozier
R A
RA
Revilla-Sanchez
R
R
Kelly
M P
MP
Dunlop
A J
AJ
Murdoch
H
H
Taylor
N
N
Xie
Y
Y
Pausch
M
M
Hayashi-Takagi
A
A
Ishizuka
K
K
Seshadri
S
S
Bates
B
B
Kariya
K
K
Sawa
A
A
Weinberg
R J
RJ
Moss
S J
SJ
Houslay
M D
MD
Yan
Z
Z
Brandon
N J
NJ
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*
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