Follice-stimulating hormone receptor forms oligomers and shows evidence of carboxyl-terminal proteolytic processing.

FSH receptor (FSHR), a member of the G protein-coupled receptor superfamily, is present in the plasma membrane of ovarian granulosa cells and testicular Sertoli cells. FSH regulates normal ovarian follicle development and spermatogenesis through FSHR. The extracellular domain of FSHR is a weakly associated homodimer in the recently solved crystal structure of FSH in complex with the extracellular domain of FSHR. However, there is currently no biochemical data that demonstrate that FSHR exists as a dimer or higher-order oligomer in cell membranes. A fluorescence resonance energy transfer assay was used to determine whether full-length native FSHR is an oligomer. FSHR-specific monoclonal antibody or Fab fragments, labeled with two different fluorophores, allowed the study of nontagged receptor in situ. Unoccupied FSHR exhibited strong fluorescence resonance energy transfer profiles in situ. Complementary coimmunoprecipitation experiments of myc- or FLAG-tagged FSHR indicated that FSHR forms oligomers early ...