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PLoS One. 2010 May 28;5(5):e10902. doi: 10.1371/journal.pone.0010902.

DISC1 regulates primary cilia that display specific dopamine receptors.

Author information

1
Department of Psychiatry, University of California San Francisco, San Francisco, California, United States of America.

Abstract

BACKGROUND:

Mutations in the DISC1 gene are strongly associated with major psychiatric syndromes such as schizophrenia. DISC1 encodes a cytoplasmic protein with many potential interaction partners, but its cellular functions remain poorly understood. We identified a role of DISC1 in the cell biology of primary cilia that display disease-relevant dopamine receptors.

METHODOLOGY/PRINCIPAL FINDINGS:

A GFP-tagged DISC1 construct expressed in NIH3T3 cells and rat striatal neurons localized near the base of primary cilia. RNAi-mediated knockdown of endogenous DISC1 resulted in a marked reduction in the number of cells expressing a primary cilium. FLAG-tagged versions of the cloned human D1, D2 and D5 dopamine receptors concentrated highly on the ciliary surface, and this reflects a specific targeting mechanism specific because D3 and D4 receptors localized to the plasma membrane but were not concentrated on cilia.

CONCLUSIONS/SIGNIFICANCE:

These results identify a role of DISC1 in regulating the formation and/or maintenance of primary cilia, and establish subtype-specific targeting of dopamine receptors to the ciliary surface. Our findings provide new insight to receptor cell biology and suggest a relationship between DISC1 and neural dopamine signaling.

PMID:
20531939
PMCID:
PMC2878344
DOI:
10.1371/journal.pone.0010902
[Indexed for MEDLINE]
Free PMC Article

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