Editors' ChoicePheromones

Making Scents of Atypical MHC Genes

STKE  18 Mar 2003:
Vol. 2003, Issue 174, pp. tw108-TW108
DOI: 10.1126/stke.2003.174.tw108

In mammals, pheromones--chemical cues that trigger mating and social behaviors--are detected through two large families of heterotrimeric guanine nucleotide-binding protein-coupled receptors (GPCRs), V1R and V2R, expressed in sensory neurons in discreet regions of the vomeronasal organ (VNO). The molecular mechanisms through which diversity and specificity of pheromone responses are achieved, however, have remained unclear. Loconto et al. used subtractive differential screening of cDNA libraries from individual rat VNO neurons and isolated a nonclassical major histocompatibility complex (MHC) class Ib gene. The authors used a combination of techniques including in situ hybridization, single-cell reverse transcription polymerase chain reaction (RT-PCR), immunocytochemistry, and transgenic analysis to investigate the association of M10.7, the mouse homolog of this gene, with pheromone receptors. M10.7 and the five other presumably functional members of the M10 gene family were expressed exclusively in V2R-expressing neurons in the basal neuroepithelium of the VNO. Particular V2Rs specifically associated with one or a few members of the M10 family. Western analysis in combination with immunoaffinity chromatography indicated that V2R, M10, and β2-microglobulin (β2m), which generally associates with MHC molecules, formed a multimolecular complex. In vitro experiments indicated that this association was required for V2R localization to the plasma membrane. Moreover, transgenic mice lacking β2m showed V2R mislocalization and lacked typical male-male aggressive behavior. The authors speculated that M10, in addition to escorting V2R to the cell surface, may alter the mechanism and specificity of pheromone recognition by heterodimerizing with the V2R.

J. Loconto, F. Papes, E. Chang, L. Stowers, E. P. Jones, T. Takada, A. Kumánovics, K. F. Lindahl, C. Dulac, Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell 112, 607-618 (2003). [Online Journal]