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PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia.

Publication ,  Journal Article
Monroe, TO; Garrett, ME; Kousi, M; Rodriguiz, RM; Moon, S; Bai, Y; Brodar, SC; Soldano, KL; Savage, J; Hansen, TF; Muzny, DM; Gibbs, RA ...
Published in: Nat Commun
November 19, 2020

The neuronal primary cilium and centriolar satellites have functions in neurogenesis, but little is known about their roles in the postnatal brain. We show that ablation of pericentriolar material 1 in the mouse leads to progressive ciliary, anatomical, psychomotor, and cognitive abnormalities. RNAseq reveals changes in amine- and G-protein coupled receptor pathways. The physiological relevance of this phenotype is supported by decreased available dopamine D2 receptor (D2R) levels and the failure of antipsychotic drugs to rescue adult behavioral defects. Immunoprecipitations show an association with Pcm1 and D2Rs. Finally, we sequence PCM1 in two human cohorts with severe schizophrenia. Systematic modeling of all discovered rare alleles by zebrafish in vivo complementation reveals an enrichment for pathogenic alleles. Our data emphasize a role for the pericentriolar material in the postnatal brain, with progressive degenerative ciliary and behavioral phenotypes; and they support a contributory role for PCM1 in some individuals diagnosed with schizophrenia.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 19, 2020

Volume

11

Issue

1

Start / End Page

5903

Location

England

Related Subject Headings

  • Zebrafish
  • Young Adult
  • Signal Transduction
  • Schizophrenia
  • Receptors, G-Protein-Coupled
  • Receptors, Dopamine D2
  • Phenotype
  • Mutation
  • Middle Aged
  • Mice, Knockout
 

Citation

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Monroe, T. O., Garrett, M. E., Kousi, M., Rodriguiz, R. M., Moon, S., Bai, Y., … Katsanis, N. (2020). PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia. Nat Commun, 11(1), 5903. https://doi.org/10.1038/s41467-020-19637-5
Monroe, Tanner O., Melanie E. Garrett, Maria Kousi, Ramona M. Rodriguiz, Sungjin Moon, Yushi Bai, Steven C. Brodar, et al. “PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia.Nat Commun 11, no. 1 (November 19, 2020): 5903. https://doi.org/10.1038/s41467-020-19637-5.
Monroe TO, Garrett ME, Kousi M, Rodriguiz RM, Moon S, Bai Y, et al. PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia. Nat Commun. 2020 Nov 19;11(1):5903.
Monroe, Tanner O., et al. “PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia.Nat Commun, vol. 11, no. 1, Nov. 2020, p. 5903. Pubmed, doi:10.1038/s41467-020-19637-5.
Monroe TO, Garrett ME, Kousi M, Rodriguiz RM, Moon S, Bai Y, Brodar SC, Soldano KL, Savage J, Hansen TF, Muzny DM, Gibbs RA, Barak L, Sullivan PF, Ashley-Koch AE, Sawa A, Wetsel WC, Werge T, Katsanis N. PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia. Nat Commun. 2020 Nov 19;11(1):5903.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 19, 2020

Volume

11

Issue

1

Start / End Page

5903

Location

England

Related Subject Headings

  • Zebrafish
  • Young Adult
  • Signal Transduction
  • Schizophrenia
  • Receptors, G-Protein-Coupled
  • Receptors, Dopamine D2
  • Phenotype
  • Mutation
  • Middle Aged
  • Mice, Knockout