Cellular and Molecular Life Sciences

, Volume 68, Issue 17, pp 2951–2960

Dopamine receptor 1 localizes to neuronal cilia in a dynamic process that requires the Bardet-Biedl syndrome proteins

  • Jacqueline S. Domire
  • Jill A. Green
  • Kirsten G. Lee
  • Andrew D. Johnson
  • Candice C. Askwith
  • Kirk Mykytyn
Research Article

DOI: 10.1007/s00018-010-0603-4

Cite this article as:
Domire, J.S., Green, J.A., Lee, K.G. et al. Cell. Mol. Life Sci. (2011) 68: 2951. doi:10.1007/s00018-010-0603-4

Abstract

Primary cilia are nearly ubiquitous cellular appendages that provide important sensory and signaling functions. Ciliary dysfunction underlies numerous human diseases, collectively termed ciliopathies. Primary cilia have distinct functions on different cell types and these functions are defined by the signaling proteins that localize to the ciliary membrane. Neurons throughout the mammalian brain possess primary cilia upon which certain G protein-coupled receptors localize. Yet, the precise signaling proteins present on the vast majority of neuronal cilia are unknown. Here, we report that dopamine receptor 1 (D1) localizes to cilia on mouse central neurons, thereby implicating neuronal cilia in dopamine signaling. Interestingly, ciliary localization of D1 is dynamic, and the receptor rapidly translocates to and from cilia in response to environmental cues. Notably, the translocation of D1 from cilia requires proteins mutated in the ciliopathy Bardet-Biedl syndrome (BBS), and we find that one of the BBS proteins, Bbs5, specifically interacts with D1.

Keywords

CiliopathyNeuronal ciliaDopamine receptor 1Bardet-Biedl syndrome

Abbreviations

BBS

Bardet-Biedl syndrome

GPCR

G protein-coupled receptor

D1

Dopamine receptor 1

Mchr1

Melanin-concentrating hormone receptor 1

Sstr3

Somatostatin receptor 3

ACIII

Type III adenylyl cyclase

IMCD

Inner medullary collecting duct

i3

Third intracellular

C-tail

Carboxy terminal tail

Supplementary material

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Supplementary material 1 (DOC 34 kb)
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Supplementary material 5 (TIFF 285 kb)
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Supplementary material 6 (TIFF 248 kb)

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Jacqueline S. Domire
    • 1
  • Jill A. Green
    • 1
  • Kirsten G. Lee
    • 2
  • Andrew D. Johnson
    • 3
  • Candice C. Askwith
    • 2
  • Kirk Mykytyn
    • 1
  1. 1.Department of Pharmacology, College of MedicineThe Ohio State UniversityColumbusUSA
  2. 2.Department of Neuroscience, College of MedicineThe Ohio State UniversityColumbusUSA
  3. 3.The National Heart, Lung and Blood Institute’s Framingham Heart StudyCenter for Population StudiesFraminghamUSA