TY - JOUR
T1 - Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules
AU - Loconto, Jennifer
AU - Papes, Fabio
AU - Chang, Ernie
AU - Stowers, Lisa
AU - Jones, Elsy P.
AU - Takada, Toyoyuki
AU - Kumánovics, Attila
AU - Lindahl, Kirsten Fischer
AU - Dulac, Catherine
N1 - Funding Information:
We wish to acknowledge Renate Hellmiss-Peralta for artistic work and illustrations and Cecilia Lee for help with the manuscript. We thank Jolanta Dubauskaite for mouse transgenic work; Gilles Herrada, Shlomo Wagner, and Lorena Pont-Lezica for providing unpublished reagents and useful advice; M.E. Klein, Qiarong Jiang, and Enxi Chu for technical assistance; and Drs. Jack Strominger, Richard Axel, and Carla Schatz for helpful discussions. Plasmid pS521 was kindly provided by Dr. P. Schneider. Anti-VN2 and anti-VN4 rabbit antisera were obtained from Dr. Roberto Tirindelli and anti-rhodopsin from Drs. Randy Reed, Jeremy Nathans, and Paul Hargrave. This work was supported by the Howard Hughes Medical Institute, and by grants 3903-01 of NIH-NIDCD (C.D.) and AI37818 of NIH (K.F.L.).
PY - 2003/3/7
Y1 - 2003/3/7
N2 - The vomeronasal organ (VNO) of the mouse has two neuronal compartments expressing distinct families of pheromone receptors, the V1Rs and the V2Rs. We report here that two families of major histocompatibility complex (MHC) class Ib molecules, the M10 and the M1 families, show restricted expression in V2R-expressing neurons. Our data suggest that neurons expressing a given V2R specifically co-express one or a few members of the M10 family. Biochemical and immunocytochemical analysis demonstrates that in VNO sensory dendrites M10s belong to large multi-molecular complexes that include pheromone receptors and β2-microglobulin (β2m). In cultured cells, M10s appear to function as escort molecules in transport of V2Rs to the cell surface. Accordingly, β2m-deficient mice exhibit mislocalization of V2Rs in the VNO and a specific defect in male-male aggressive behavior. The functional characterization of M10 highlights an unexpected role for MHC molecules in pheromone detection by mammalian VNO neurons.
AB - The vomeronasal organ (VNO) of the mouse has two neuronal compartments expressing distinct families of pheromone receptors, the V1Rs and the V2Rs. We report here that two families of major histocompatibility complex (MHC) class Ib molecules, the M10 and the M1 families, show restricted expression in V2R-expressing neurons. Our data suggest that neurons expressing a given V2R specifically co-express one or a few members of the M10 family. Biochemical and immunocytochemical analysis demonstrates that in VNO sensory dendrites M10s belong to large multi-molecular complexes that include pheromone receptors and β2-microglobulin (β2m). In cultured cells, M10s appear to function as escort molecules in transport of V2Rs to the cell surface. Accordingly, β2m-deficient mice exhibit mislocalization of V2Rs in the VNO and a specific defect in male-male aggressive behavior. The functional characterization of M10 highlights an unexpected role for MHC molecules in pheromone detection by mammalian VNO neurons.
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U2 - 10.1016/S0092-8674(03)00153-3
DO - 10.1016/S0092-8674(03)00153-3
M3 - Article
C2 - 12628182
AN - SCOPUS:0037423953
SN - 0092-8674
VL - 112
SP - 607
EP - 618
JO - Cell
JF - Cell
IS - 5
ER -