Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: A candidate for psychiatric illnesses

Atsushi Kamiya, Perciliz L. Tan, Kenichiro Kubo, Caitlin Engelhard, Koko Ishizuka, Akiharu Kubo, Sachiko Tsukita, Ann E. Pulver, Kazunori Nakajima, Nicola G. Cascella, Nicholas Katsanis, Ahira Sawa

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Context: A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ). Objectives: To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population. Design: Interaction of DISC1, PCM1, and BBS proteins was assessed by immunofluorescent staining and coimmunoprecipitation. Effects of PCM1, DISC1, and BBS on centrosomal functions and corticogenesis in vivo were tested by RNA interference. The PCM1 gene was examined by sequencing 39 exons and flanking splice sites. Setting: Probands and controls were from the collection of one of us (A.E.P.). Patients: Thirty-two probands with SZ from families that had excess allele sharing among affected individuals at 8p22 and 219 white controls. Main Outcome Measures: Protein interaction and recruitment at the centrosome in cells; neuronal migration in the cerebral cortex; and variant discovery in PCM1 in patients with SZ. Results: PCM1 forms a complex with DISCf and BBS4 through discrete binding domains in each protein. DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner. In the developing cerebral cortex, suppression of PCM1 leads to neuronal migration defects, which are phenocopied by the suppression of either DISC1 or BBS4 and are exacerbated by the concomitant suppression of both. Furthermore, a nonsense mutation that segregates with SZ spectrum psychosis was found in 1 family. Conclusions: Our data further support for the role of centrosomal proteins in cortical development and suggest that perturbation of centrosomal function contributes to the development of mental diseases, including SZ.

Original languageEnglish
Pages (from-to)996-1006
Number of pages11
JournalArchives of General Psychiatry
Volume65
Issue number9
DOIs
Publication statusPublished - 2008 Sep

Fingerprint

Centrosome
Staphylococcal Protein A
Psychiatry
Schizophrenia
Proteins
Bardet-Biedl syndrome 4
Cerebral Cortex
Pathology
Nonsense Codon
Protein Transport

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4 : A candidate for psychiatric illnesses. / Kamiya, Atsushi; Tan, Perciliz L.; Kubo, Kenichiro; Engelhard, Caitlin; Ishizuka, Koko; Kubo, Akiharu; Tsukita, Sachiko; Pulver, Ann E.; Nakajima, Kazunori; Cascella, Nicola G.; Katsanis, Nicholas; Sawa, Ahira.

In: Archives of General Psychiatry, Vol. 65, No. 9, 09.2008, p. 996-1006.

Research output: Contribution to journalArticle

Kamiya, A, Tan, PL, Kubo, K, Engelhard, C, Ishizuka, K, Kubo, A, Tsukita, S, Pulver, AE, Nakajima, K, Cascella, NG, Katsanis, N & Sawa, A 2008, 'Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: A candidate for psychiatric illnesses', Archives of General Psychiatry, vol. 65, no. 9, pp. 996-1006. https://doi.org/10.1001/archpsyc.65.9.996
Kamiya, Atsushi ; Tan, Perciliz L. ; Kubo, Kenichiro ; Engelhard, Caitlin ; Ishizuka, Koko ; Kubo, Akiharu ; Tsukita, Sachiko ; Pulver, Ann E. ; Nakajima, Kazunori ; Cascella, Nicola G. ; Katsanis, Nicholas ; Sawa, Ahira. / Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4 : A candidate for psychiatric illnesses. In: Archives of General Psychiatry. 2008 ; Vol. 65, No. 9. pp. 996-1006.
@article{e947e70b422e46ae9947b7b5a30c93c8,
title = "Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: A candidate for psychiatric illnesses",
abstract = "Context: A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ). Objectives: To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population. Design: Interaction of DISC1, PCM1, and BBS proteins was assessed by immunofluorescent staining and coimmunoprecipitation. Effects of PCM1, DISC1, and BBS on centrosomal functions and corticogenesis in vivo were tested by RNA interference. The PCM1 gene was examined by sequencing 39 exons and flanking splice sites. Setting: Probands and controls were from the collection of one of us (A.E.P.). Patients: Thirty-two probands with SZ from families that had excess allele sharing among affected individuals at 8p22 and 219 white controls. Main Outcome Measures: Protein interaction and recruitment at the centrosome in cells; neuronal migration in the cerebral cortex; and variant discovery in PCM1 in patients with SZ. Results: PCM1 forms a complex with DISCf and BBS4 through discrete binding domains in each protein. DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner. In the developing cerebral cortex, suppression of PCM1 leads to neuronal migration defects, which are phenocopied by the suppression of either DISC1 or BBS4 and are exacerbated by the concomitant suppression of both. Furthermore, a nonsense mutation that segregates with SZ spectrum psychosis was found in 1 family. Conclusions: Our data further support for the role of centrosomal proteins in cortical development and suggest that perturbation of centrosomal function contributes to the development of mental diseases, including SZ.",
author = "Atsushi Kamiya and Tan, {Perciliz L.} and Kenichiro Kubo and Caitlin Engelhard and Koko Ishizuka and Akiharu Kubo and Sachiko Tsukita and Pulver, {Ann E.} and Kazunori Nakajima and Cascella, {Nicola G.} and Nicholas Katsanis and Ahira Sawa",
year = "2008",
month = "9",
doi = "10.1001/archpsyc.65.9.996",
language = "English",
volume = "65",
pages = "996--1006",
journal = "JAMA Psychiatry",
issn = "2168-622X",
publisher = "American Medical Association",
number = "9",

}

TY - JOUR

T1 - Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4

T2 - A candidate for psychiatric illnesses

AU - Kamiya, Atsushi

AU - Tan, Perciliz L.

AU - Kubo, Kenichiro

AU - Engelhard, Caitlin

AU - Ishizuka, Koko

AU - Kubo, Akiharu

AU - Tsukita, Sachiko

AU - Pulver, Ann E.

AU - Nakajima, Kazunori

AU - Cascella, Nicola G.

AU - Katsanis, Nicholas

AU - Sawa, Ahira

PY - 2008/9

Y1 - 2008/9

N2 - Context: A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ). Objectives: To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population. Design: Interaction of DISC1, PCM1, and BBS proteins was assessed by immunofluorescent staining and coimmunoprecipitation. Effects of PCM1, DISC1, and BBS on centrosomal functions and corticogenesis in vivo were tested by RNA interference. The PCM1 gene was examined by sequencing 39 exons and flanking splice sites. Setting: Probands and controls were from the collection of one of us (A.E.P.). Patients: Thirty-two probands with SZ from families that had excess allele sharing among affected individuals at 8p22 and 219 white controls. Main Outcome Measures: Protein interaction and recruitment at the centrosome in cells; neuronal migration in the cerebral cortex; and variant discovery in PCM1 in patients with SZ. Results: PCM1 forms a complex with DISCf and BBS4 through discrete binding domains in each protein. DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner. In the developing cerebral cortex, suppression of PCM1 leads to neuronal migration defects, which are phenocopied by the suppression of either DISC1 or BBS4 and are exacerbated by the concomitant suppression of both. Furthermore, a nonsense mutation that segregates with SZ spectrum psychosis was found in 1 family. Conclusions: Our data further support for the role of centrosomal proteins in cortical development and suggest that perturbation of centrosomal function contributes to the development of mental diseases, including SZ.

AB - Context: A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ). Objectives: To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population. Design: Interaction of DISC1, PCM1, and BBS proteins was assessed by immunofluorescent staining and coimmunoprecipitation. Effects of PCM1, DISC1, and BBS on centrosomal functions and corticogenesis in vivo were tested by RNA interference. The PCM1 gene was examined by sequencing 39 exons and flanking splice sites. Setting: Probands and controls were from the collection of one of us (A.E.P.). Patients: Thirty-two probands with SZ from families that had excess allele sharing among affected individuals at 8p22 and 219 white controls. Main Outcome Measures: Protein interaction and recruitment at the centrosome in cells; neuronal migration in the cerebral cortex; and variant discovery in PCM1 in patients with SZ. Results: PCM1 forms a complex with DISCf and BBS4 through discrete binding domains in each protein. DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner. In the developing cerebral cortex, suppression of PCM1 leads to neuronal migration defects, which are phenocopied by the suppression of either DISC1 or BBS4 and are exacerbated by the concomitant suppression of both. Furthermore, a nonsense mutation that segregates with SZ spectrum psychosis was found in 1 family. Conclusions: Our data further support for the role of centrosomal proteins in cortical development and suggest that perturbation of centrosomal function contributes to the development of mental diseases, including SZ.

UR - http://www.scopus.com/inward/record.url?scp=50949092420&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50949092420&partnerID=8YFLogxK

U2 - 10.1001/archpsyc.65.9.996

DO - 10.1001/archpsyc.65.9.996

M3 - Article

C2 - 18762586

AN - SCOPUS:50949092420

VL - 65

SP - 996

EP - 1006

JO - JAMA Psychiatry

JF - JAMA Psychiatry

SN - 2168-622X

IS - 9

ER -