TY - JOUR
T1 - S100B Serves as a Ca 2+ sensor for ROS-GC1 guanylate cyclase in cones but not in rods of the murine retina
AU - Wen, Xiao Hong
AU - Duda, Teresa
AU - Pertzev, Alexandre
AU - Venkataraman, Venkateswar
AU - Makino, Clint L.
AU - Sharma, Rameshwar K.
PY - 2012/4
Y1 - 2012/4
N2 - Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca 2+ signal transduction switch. Lowering [Ca 2+ ] i from 200 to 20 nM progressively turns it "ON" as does raising [Ca 2+ ] i from 500 to 5000 nM. The mode operating at lower [Ca 2+ ] i plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated [Ca 2+ ] i is not known. Through comprehensive studies on mice involving gene deletions, biochemistry, immunohistochemistry, electroretinograms and single cell recordings, the present study demonstrates that the Ca 2+ -sensor S100B coexists with and is physiologically linked to ROS-GC1 in cones but not in rods. It up-regulates ROS-GC1 activity with a K 1/2 for Ca 2+ greater than 500 nM and modulates the transmission of neural signals to cone ON-bipolar cells. Furthermore, a possibility is raised that under pathological conditions where [Ca 2+ ] i levels rise to and perhaps even enter the micromolar range, the S100B signaling switch will be turned "ON" causing an explosive production of CNG channel opening and further rise in [Ca 2+ ] i in cone outer segments. The findings define a new cone-specific Ca 2+ -dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery.
AB - Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca 2+ signal transduction switch. Lowering [Ca 2+ ] i from 200 to 20 nM progressively turns it "ON" as does raising [Ca 2+ ] i from 500 to 5000 nM. The mode operating at lower [Ca 2+ ] i plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated [Ca 2+ ] i is not known. Through comprehensive studies on mice involving gene deletions, biochemistry, immunohistochemistry, electroretinograms and single cell recordings, the present study demonstrates that the Ca 2+ -sensor S100B coexists with and is physiologically linked to ROS-GC1 in cones but not in rods. It up-regulates ROS-GC1 activity with a K 1/2 for Ca 2+ greater than 500 nM and modulates the transmission of neural signals to cone ON-bipolar cells. Furthermore, a possibility is raised that under pathological conditions where [Ca 2+ ] i levels rise to and perhaps even enter the micromolar range, the S100B signaling switch will be turned "ON" causing an explosive production of CNG channel opening and further rise in [Ca 2+ ] i in cone outer segments. The findings define a new cone-specific Ca 2+ -dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery.
UR - http://www.scopus.com/inward/record.url?scp=84859927297&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859927297&partnerID=8YFLogxK
U2 - 10.1159/000338496
DO - 10.1159/000338496
M3 - Article
C2 - 22508049
AN - SCOPUS:84859927297
SN - 1015-8987
VL - 29
SP - 417
EP - 430
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
IS - 3-4
ER -