S100B Serves as a Ca2+ Sensor for ROS-GC1 Guanylate Cyclase in Cones but not in Rods of the Murine RetinaWen X.-H.1,* · Duda T.2,* · Pertzev A.2 · Venkataraman V.3 · Makino C.L.1 · Sharma R.K.2
1Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, MA,2Research Divisions of Biochemistry and Molecular Biology, The Unit of Regulatory and Molecular Biology, Salus University, Elkins Park, PA,3Department of Cell Biology, University of Medicine and Dentistry of New Jersey-SOM, Stratford, NJ,*Xiao-Hong Wen and Teresa Duda contributed equally to this work Corresponding Author
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary
and Harvard Medical School, 243 Charles Street, Boston, MA 02114 (USA)
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Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca2+ signal transduction switch. Lowering [Ca2+]i from 200 to 20 nM progressively turns it “ON” as does raising [Ca2+]i from 500 to 5000 nM. The mode operating at lower [Ca2+]i plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated [Ca2+]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 Ca2+-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 K1/2 for Ca2+ 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 [Ca2+]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 [Ca2+]i in cone outer segments. The findings define a new cone-specific Ca2+-dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery.
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