Disrupted-in-schizophrenia-1 (DISC1) Regulates Endoplasmic Reticulum Calcium Dynamics

Sung Jin Park, Jaehoon Jeong, Young Un Park, Kyung Sun Park, Haeryun Lee, Namgyu Lee, Sung Mo Kim, Keisuke Kuroda, Minh Dang Nguyen, Kozo Kaibuchi, Sang Ki Park

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Disrupted-in-schizophrenia-1 (DISC1) has emerged as a convincing susceptibility gene for multiple mental disorders, but its mechanistic link to the pathogenesis of schizophrenia related psychiatric conditions is yet to be further understood. Here, we showed that DISC1 localizes to the outer surface of the endoplasmic reticulum (ER). EXOC1, a subunit of the exocyst complex, interacted with DISC1 and affected its recruitment to inositol-1,4,5-trisphosphate receptor 1 (IP3R1). Notably, knockdown of DISC1 and EXOC1 elicited an exaggerated ER calcium response upon stimulation of IP3R agonists. Similar abnormal ER calcium responses were observed in hippocampal neurons from DISC1-deficient mutant mice. Moreover, perturbation of ER calcium dynamics upon DISC1 knockdown was effectively reversed by treatment with antipsychotic drugs, such as clozapine and haloperidol. These results collectively indicate that DISC1 is a regulatory factor in ER calcium dynamics, linking a perturbed intracellular calcium signaling and schizophrenia pathogenesis.

Original languageEnglish
Article number8694
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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