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Proc Natl Acad Sci U S A

Title:		Calreticulin chaperones regulate functional expression of vomeronasal type 2 pheromone receptors
Author(s):		Dey S; Matsunami H;
Address:		"Department of Molecular Genetics and Microbiology, Duke Institute for Brain Sciences, Duke University Medical Center, Durham, NC 27710, USA"
Journal Title:		Proc Natl Acad Sci U S A
Year:		2011
Volume:		20110920
Issue:		40
Page Number:		16651 - 16656
DOI:		10.1073/pnas.1018140108
ISSN/ISBN:		1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking)
Abstract:		"A variety of social behaviors like intermale aggression, fear, and mating rituals are important for sustenance of a species. In mice, these behaviors have been implicated to be mediated by peptide pheromones that are sensed by a class of G protein-coupled receptors, vomeronasal receptor type 2 (V2Rs), expressed in the pheromone detecting vomeronasal organ. Matching V2Rs with their cognate ligands is required to learn what receptors the biologically relevant pheromones are acting on. However, this feat has been greatly limited by the unavailability of appropriate heterologous tools commonly used to study ligand receptor specificity, because this family of receptors fails to traffic to the surface of heterologous cells. Here we show that calreticulin, a housekeeping chaperone commonly expressed in most eukaryotic cells, is sparsely expressed in the vomeronasal sensory neurons (VSNs). Correspondingly, knockdown of calreticulin in commonly available cell lines enables V2Rs to efficiently target to the cell membrane. Using this knowledge, we have now been able to successfully surface express receptors and functionally identify cognate ligands. Additionally, calreticulin4, a homolog of calreticulin shows restricted and enriched expression in the VSNs. Interestingly, in heterologous cells, calreticulin4 does not inhibit surface expression of V2Rs and can in part carry out functions of calreticulin. On the basis of our data, we postulate that V2Rs may use a unique trafficking mechanism whereby an important and more commonly expressed chaperone is deleterious for membrane export and is replaced by a functionally equivalent homolog that does not inhibit export while carrying out its functions"
Keywords:		"Animals Base Sequence Blotting, Western Calreticulin/*genetics/*metabolism Cell Line DNA Primers/genetics Gene Knockdown Techniques Humans Immunohistochemistry Immunoprecipitation In Situ Hybridization Mice Mice, Inbred C57BL Molecular Chaperones/*metabol;"
Notes:		"MedlineDey, Sandeepa Matsunami, Hiroaki eng R01 DC005782/DC/NIDCD NIH HHS/ R01 DC010857/DC/NIDCD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2011/09/22 Proc Natl Acad Sci U S A. 2011 Oct 4; 108(40):16651-6. doi: 10.1073/pnas.1018140108. Epub 2011 Sep 20"