Disrupted-in-schizophrenia 1 (DISC1) Regulates Dysbindin Function by Enhancing Its Stability

作者：Lee Seol Ae; Kim Seong Mo; Suh Bo Kyoung; Sun Hwa Young; Park Young Un; Hong Ji Ho; Park Cana; Minh Dang Nguyen; Nagata Koh ichi; Yoo Joo Yeon; Park Sang Ki^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290(11): 7087-7096.

DOI：10.1074/jbc.M114.614750

Dysbindin and DISC1 are schizophrenia susceptibility factors playing roles in neuronal development. Here we show that the physical interaction between dysbindin and DISCI is critical for the stability of dysbindin and for the process of neurite outgrowth. We found that DISCI forms a complex with dysbindin and increases its stability in association with a reduction in ubiquitylation. Furthermore, knockdown of DISCI or expression of a deletion mutant, DISCI lacking amino acid residues 403-504 of DISC1 (DISC1(Delta 403-504)), effectively decreased levels of endogenous dysbindin. Finally, the neurite outgrowth defect induced by knockdown of DISCI was partially reversed by coexpression of dysbindin. Taken together, these results indicate that dysbindin and DISC1 form a physiologically functional complex that is essential for normal neurite outgrowth.

• 出版日期2015-3-13