Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules.
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 beta2-microglobulin (beta2m). In cultured cells, M10s appear to function as escort molecules in transport of V2Rs to the cell surface. Accordingly, beta2m-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.
Loconto
Jennifer
J
Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Papes
Fabio
F
Chang
Ernie
E
Stowers
Lisa
L
Jones
Elsy P
EP
Takada
Toyoyuki
T
Kumánovics
Attila
A
Fischer Lindahl
Kirsten
K
Dulac
Catherine
C
D000374:Aggression / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012724:Sex Attractants / Q000378:metabolism; D012919:Social Behavior; D019147:Vomeronasal Organ / Q000166:cytology / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics
D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D012724:Sex Attractants; D001613:beta 2-Microglobulin