TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade.
An essential step in intricate visual processing is the segregation of visual signals into ON and OFF pathways by retinal bipolar cells (BCs). Glutamate released from photoreceptors modulates the photoresponse of ON BCs via metabotropic glutamate receptor 6 (mGluR6) and G protein (Go) that regulates a cation channel. However, the cation channel has not yet been unequivocally identified. Here, we report a mouse TRPM1 long form (TRPM1-L) as the cation channel. We found that TRPM1-L localization is developmentally restricted to the dendritic tips of ON BCs in colocalization with mGluR6. TRPM1 null mutant mice completely lose the photoresponse of ON BCs but not that of OFF BCs. In the TRPM1-L-expressing cells, TRPM1-L functions as a constitutively active nonselective cation channel and its activity is negatively regulated by Go in the mGluR6 cascade. These results demonstrate that TRPM1-L is a component of the ON BC transduction channel downstream of mGluR6 in ON BCs.
Koike
Chieko
C
Department of Developmental Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
Obara
Takehisa
T
Uriu
Yoshitsugu
Y
Numata
Tomohiro
T
Sanuki
Rikako
R
Miyata
Kentarou
K
Koyasu
Toshiyuki
T
Ueno
Shinji
S
Funabiki
Kazuo
K
Tani
Akiko
A
Ueda
Hiroshi
H
Kondo
Mineo
M
Mori
Yasuo
Y
Tachibana
Masao
M
Furukawa
Takahisa
T
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004594:Electrophysiology; D006801:Humans; D008027:Light; D055537:Light Signal Transduction / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000502:physiology*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D018094:Receptors, Metabotropic Glutamate; D050053:TRPM Cation Channels; C116297:Trpm1 protein, mouse; C113897:metabotropic glutamate receptor 6