title: S100B serves as a Ca(2+) sensor for ROS-GC1 guanylate cyclase in cones but not in rods of the murine retina.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, MA 02114, USA. wenx@meei.harvard.edu
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wen
authors.forename: Teresa
authors.initials: T
authors.lastname: Duda
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pertzev
authors.forename: Venkateswar
authors.initials: V
authors.lastname: Venkataraman
authors.forename: Clint L
authors.initials: CL
authors.lastname: Makino
authors.forename: Rameshwar K
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D055537:Light Signal Transduction; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D012374:Rod Cell Outer Segment / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D013570:Synaptic Membranes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology
chemical_list: D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium