DISC1 localizes to the centrosome by binding to kendrin.
Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation that segregated with major mental disorders in a Scottish family. Using the yeast two-hybrid system, we screened a human brain cDNA library for interactors of the DISC1 protein. One of the positive clones encoded kendrin/pericentrin-B, a giant protein known to localize specifically to the centrosome. The interaction between DISC1 and kendrin in mammalian cells was demonstrated by an immunoprecipitation assay. Residues 446-533 of DISC1 were essential for the interaction with kendrin. Immunocytochemical analysis revealed the colocalization of DISC1 and kendrin to the centrosome. These data indicate that DISC1 localizes to the centrosome by binding to kendrin. Kendrin has been reported to anchor the gamma-tubulin complex to the centrosome, providing microtubule nucleation sites. The present study suggests the possible involvement of DISC1 in the pathophysiology of mental disorders due to its putative effect on centrosomal function.
Miyoshi
Ko
K
Department of Brain Science, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558, Japan. miyoshi@cc.okayama-u.ac.jp
Asanuma
Masato
M
Miyazaki
Ikuko
I
Diaz-Corrales
Francisco J
FJ
Katayama
Taiichi
T
Tohyama
Masaya
M
Ogawa
Norio
N
D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011487:Protein Conformation; D014170:Transformation, Genetic; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
D002148:Calmodulin-Binding Proteins; C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; C410004:kendrin