|
Summary of Research Projects (Supports in 2003
Fiscal Year)
| Subjects |
Ligand-induced rearrangement of the intracellular dimeric conformation
of metabotropic glutamate receptor1a. |
| Representative researcher |
National Institute for Physiological Sciences Yoshihiro
KUBO |
| Joint researcher |
National Institute for Physiological Sciences Michihiro TATEYAMA |
| National Institute for Physiological Sciences Yuichiro FUJIWARA |
| The dimeric conformation
of the metabotropic glutamate receptor 1a (mGluR1) is a key
determinant of the downstream signaling, since crystallographic
analysis has shown that glutamate stabilize the active state
of the dimeric conformation of the extracellular domain.
We investigated the ligand-induced dimeric rearrangement
of the cytoplasmic domain by analyzing the fluorescence resonance
energy transfer (FRET) signal obtained from the plasma membrane,
where ligands interact with the mGluR1a, using a total internal
reflection field microscopy system. Intersubunit FRET efficiency
was altered within 9 s after glutamate application, while
intrasubunit FRET efficiency was not changed. The effect
was dependent on glutamate concentration, inhibited by mGluR1
antagonists and reproduced by polyvalent cations, Ca2+ and
Gd3+, which are known to activate mGluR1a. We therefore conclude
that ligand-induced rearrangement of the extracellular dimeric
conformation leads to intracellular dimeric rearrangement
without altering the respective monomeric conformations. |
|
Japanese 
returns
to the list