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

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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.

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Fig. 1a–i
Fig. 2a–c
Fig. 3
Fig. 4a, b
Fig. 5a, b

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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

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Acknowledgments

We are grateful to Joshua Stowell for technical assistance and David Sibley (NINDS) for providing D1 WT and KO brains. This work was supported in part by the Systems and Integrative Biology Training Grant T32 GM068412(J.G.) and R01 GM083120 from the NIH/National Institute of General Medical Sciences (K.M.).

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Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, The Ohio State University, 5034 Graves Hall, 333 West 10th Ave, Columbus, OH, 43210, USA

    Jacqueline S. Domire, Jill A. Green & Kirk Mykytyn

  2. Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA

    Kirsten G. Lee & Candice C. Askwith

  3. The National Heart, Lung and Blood Institute’s Framingham Heart Study, Center for Population Studies, Framingham, MA, 01702, USA

    Andrew D. Johnson

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  1. Jacqueline S. Domire
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Correspondence to Kirk Mykytyn.

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Domire, J.S., Green, J.A., Lee, K.G. et al. Dopamine receptor 1 localizes to neuronal cilia in a dynamic process that requires the Bardet-Biedl syndrome proteins. Cell. Mol. Life Sci. 68, 2951–2960 (2011). https://doi.org/10.1007/s00018-010-0603-4

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