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The Journal of Neuroscience, June 15, 2002, 22(12):4878-4884
Light Response of Retinal ON Bipolar Cells Requires a Specific
Splice Variant of G o
Anuradha
Dhingra1, *,
Meisheng
Jiang3, *,
Tian-Li
Wang1, *,
Arkady
Lyubarsky2,
Andrey
Savchenko2,
Tehilla
Bar-Yehuda1,
Peter
Sterling1,
Lutz
Birnbaumer3, and
Noga
Vardi1
Departments of 1 Neuroscience and
2 Ophthalmology, University of Pennsylvania, Philadelphia,
Pennsylvania 19104, and 3 Department of Anesthesiology,
University of California, Los Angeles, Los Angeles, California
90024
Glutamate released onto retinal ON bipolar neurons binds to a
metabotropic receptor to activate a heterotrimeric G-protein (Go) that ultimately closes a nonspecific cation
channel. Signaling requires the  subunit (Go),
but its effector is unknown. Because Go is transcribed
into two splice variants (o1 and
o2) that differ in the key GTPase domain, the
next step in elucidating this pathway was to determine which splice
variant carries the signal. Here we show by reverse transcription-PCR
and Western blots that retina expresses both splice variants.
Furthermore, in situ hybridization and immunostaining on
mouse retina deficient in one splice variant or the other show that
both o1 and o2 are expressed by ON
bipolar cells but that o1 is much more abundant. Finally, electroretinography performed on mice deficient for one splice
variant or the other shows that the positive b-wave (response of ON
bipolar cells to rod and cone input) requires o1 but not o2. Thus, the light response of the ON bipolar
cell is probably carried by its strongly expressed splice
variant, Go1.
Key words:
G-protein; Go splice variants; splice variant
knock-out mouse; mGluR6; metabotropic glutamate receptor; retina; ERG
*
A.D., M.J., and T.-L.W. contributed equally to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22124878-07$05.00/0
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