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

Scientific Reports
Sung Jin ParkSang Ki Park

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.

References

Nov 1, 1977·Psychological Medicine·A Carlsson
Feb 1, 1978·The American Journal of Psychiatry·A Carlsson
Oct 1, 1991·The American Journal of Psychiatry·D C Javitt, S R Zukin
Jan 15, 1986·The Biochemical Journal·J L Gordon
Jul 17, 1995·Biochemical and Biophysical Research Communications·I DasS R Hirsch
Jul 1, 1994·Physiological Reviews·T PozzanJ Meldolesi
Sep 15, 1996·Biological Psychiatry·S R Sczekan, F Strumwasser
Aug 11, 1998·Neuron·M J Berridge
Jun 23, 1999·Cell Calcium·S PatelA P Thomas
Jan 25, 2003·Cell Calcium·Michael J Berridge
Jan 25, 2003·Cell Calcium·J Alvarez, M Montero
Apr 1, 2003·The Journal of Biological Chemistry·Joshua H LipschutzKeith E Mostov
May 10, 2003·Nature Cell Biology·Nathalie SansRobert J Wenthold
Sep 23, 2003·Brain Research. Brain Research Reviews·Michael S Lidow
Nov 4, 2004·Journal of Receptor and Signal Transduction Research·Kim A NeveHeather Trantham-Davidson
Nov 22, 2005·Nature Cell Biology·Atsushi KamiyaAkira Sawa
Oct 21, 2006·Biochemical Society Transactions·S Wang, S C Hsu
Dec 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Asim J RashidSusan R George
Oct 4, 2007·Molecular Psychiatry·J E ChubbJ K Millar
Apr 11, 2008·Physiology·György Szabadkai, Michael R Duchen
Apr 23, 2008·Current Protocols in Neuroscience·H DudekM E Greenberg
May 16, 2008·Epidemiologic Reviews·John McGrathJoy Welham
May 22, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jyoti C PatelMargaret E Rice
Nov 6, 2009·Molecular Biology of the Cell·Nicholas J Andersen, Charles Yeaman
Feb 9, 2010·Nature Neuroscience·Akiko Hayashi-TakagiAkira Sawa
Oct 1, 2010·Proceedings of the National Academy of Sciences of the United States of America·Young-Un ParkSang Ki Park

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Citations

Jan 16, 2016·Neuroscience·Toshifumi TomodaAkira Sawa
Sep 11, 2016·Biochimica Et Biophysica Acta. Molecular Cell Research·Heike RampeltNikolaus Pfanner
Oct 30, 2016·Neuroscience Letters·Yuzuki KandaMasayuki Ikeda
Feb 18, 2017·Journal of Neurochemistry·Chihiro Hisatsune, Katsuhiko Mikoshiba
Jan 15, 2017·Schizophrenia Research·R NorkettJ T Kittler
Aug 12, 2016·Physiological Reviews·Michael J Berridge
Jul 1, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Toshifumi TomodaTakeshi Sakurai

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Methods Mentioned

BETA
Assay
transfection
immunoprecipitation
electron microscopy
co-immunoprecipitation

Software Mentioned

FV10
fluoviewer
Metamorph
Image J
MetaFluor

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