RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells.
A subset of retinal ganglion cells is intrinsically photosensitive (ipRGCs) and contributes directly to the pupillary light reflex and circadian photoentrainment under bright-light conditions. ipRGCs are also indirectly activated by light through cellular circuits initiated in rods and cones. A mammalian homologue (RdgB2) of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction is expressed in the retinal ganglion cell layer. This raised the possibility that RdgB2 might function in the intrinsic light response in ipRGCs, which depends on a cascade reminiscent of Drosophila phototransduction. Here we found that under high light intensities, RdgB2(-/-) mutant mice showed normal pupillary light responses and circadian photoentrainment. Consistent with this behavioral phenotype, the intrinsic light responses of ipRGCs in RdgB2(-/-) were indistinguishable from wild-type. In contrast, under low-light conditions, RdgB2(-/-) mutants displayed defects in both circadian photoentrainment and the pupillary light response. The RdgB2 protein was not expressed in ipRGCs but was in GABAergic amacrine cells, which provided inhibitory feedback onto bipolar cells. We propose that RdgB2 is required in a cellular circuit that transduces light input from rods to bipolar cells that are coupled to GABAergic amacrine cells and ultimately to ipRGCs, thereby enabling ipRGCs to respond to dim light.
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Marquis T
MT
Walker
Department of Biology, Johns Hopkins University, Baltimore, MD 21218.
Alan
A
Rupp
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Rebecca
R
Elsaesser
Department of Biology, Johns Hopkins University, Baltimore, MD 21218 Department of Biology, University of Virginia, Charlottesville, VA 22903.
Ali D
AD
Güler
Institute of Neurobiology, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Wenlong
W
Sheng
Institute of Neurobiology, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China Department of Neuroscience, Brown University, Providence, RI 02912.
Shijun
S
Weng
Department of Neuroscience, Brown University, Providence, RI 02912.
David M
DM
Berson
Department of Biology, Johns Hopkins University, Baltimore, MD 21218 craig.montell@lifesci.ucsb.edu shattar@jhu.edu.
Samer
S
Hattar
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205 Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara CA 93106 craig.montell@lifesci.ucsb.edu shattar@jhu.edu.
Craig
C
Montell
D000818:Animals; D002135:Calcium-Binding Proteins; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D008027:Light; D055537:Light Signal Transduction / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D012025:Reflex, Pupillary / Q000235:genetics / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism
D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; C121270:Pitpnm2 protein, mouse