Molecular Biology of the Cell

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print February 6, 2008
Mol. Biol. Cell 10.1091/mbc.E07-09-0942

A more recent version of this article appeared on April 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-09-0942v1
19/4/1540    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Berbari, N. F.
Right arrow Articles by Mykytyn, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berbari, N. F.
Right arrow Articles by Mykytyn, K.

Submitted on September 18, 2007
Revised on January 2, 2008
Accepted on January 29, 2008

Identification of Ciliary Localization Sequences within the Third Intracellular Loop of G Protein-Coupled Receptors

Nicolas F. Berbari,* Andrew D. Johnson,* Jacqueline S. Lewis,* Candice C. Askwith,{dagger} and Kirk Mykytyn*{ddagger}

*Department of Pharmacology, {dagger}Department of Neuroscience, {ddagger}Department of Internal Medicine Division of Human Genetics, and College of Medicine, The Ohio State University, Columbus, OH 43210

Monitoring Editor: Francis Barr

Primary cilia are sensory organelles present on most mammalian cells. The functions of cilia are defined by the signaling proteins localized to the ciliary membrane. Certain G protein-coupled receptors (GPCRs), including somatostatin receptor 3 (Sstr3) and serotonin receptor 6 (Htr6), localize to cilia. As Sstr3 and Htr6 are the only somatostatin and serotonin receptor subtypes that localize to cilia, we hypothesized they contain ciliary localization sequences. To test this hypothesis we expressed chimeric receptors containing fragments of Sstr3 and Htr6 in the nonciliary receptors Sstr5 and Htr7, respectively, in ciliated cells. We found the third intracellular loop of Sstr3 or Htr6 is sufficient for ciliary localization. Comparison of these loops revealed a loose consensus sequence. To determine whether this consensus sequence predicts ciliary localization of other GPCRs, we compared it against the third intracellular loop of all human GPCRs. We identified the consensus sequence in melanin-concentrating hormone receptor 1 (Mchr1) and confirmed Mchr1 localizes to primary cilia in vitro and in vivo. Thus, we have identified a putative GPCR ciliary localization sequence and used this sequence to identify a novel ciliary GPCR. As Mchr1 mediates feeding behavior and metabolism, our results implicate ciliary signaling in the regulation of body weight.

Address correspondence to: Kirk Mykytyn (mykytyn.1{at}osu.edu)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.