RGD Reference Report - DISC1 regulates primary cilia that display specific dopamine receptors. - Rat Genome Database

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DISC1 regulates primary cilia that display specific dopamine receptors.

Authors: Marley, A  Von Zastrow, M 
Citation: Marley A and von Zastrow M, PLoS One. 2010 May 28;5(5):e10902.
RGD ID: 5509786
Pubmed: PMID:20531939   (View Abstract at PubMed)
PMCID: PMC2878344   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0010902   (Journal Full-text)

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.




Biological Process

  
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Original Reference(s)
Disc1Ratcilium assembly  IMP  RGD 


Genes (Rattus norvegicus)
Disc1  (DISC1 scaffold protein)