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Neurocalcin delta modulation of ROS-GC1, a new model of Ca2+ signaling

  1. Author:
    Venkataraman, V.
    Duda, T.
    Ravichandran, S.
    Sharma, R. K.
  2. Author Address

    Duda, Teresa, Sharma, Rameshwar K.] Penn Coll Optometry, Div Biochem & Mol Biol, Unit Regulatory & Mol Biol, Elkins Pk, PA 19027 USA. [Venkataraman, Venkateswar] Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Cell Biol, Stratford, NJ 08084 USA. [Ravichandran, Sarangan] SAIC Frederick, Natl Canc Inst, Adv Biomed Computing Ctr, Frederick, MD 21702 USA.
    1. Year: 2008
  1. Journal: Biochemistry
    1. 47
    2. 25
    3. Pages: 6590-6601
  2. Type of Article: Article
  1. Abstract:

    ROS-GC1 membrane guanylate cyclase is a Ca2+ bimodal signal transduction switch. It is turned "off" by a rise in free Ca2+ from nanomolar to the semicromolar range in the photoreceptor outer segments and the olfactory bulb neurons, by a similar rise in the bipolar and ganglion retinal neurons it is turned "on". These opposite operational modes of the switch are specified by its Ca2+ sensing devices, respectively termed GCAPs and CD-GCAPs. Neurocalcin delta is a CD-GCAP. In the present study, the neurocalcin delta-modulated site, V-837-L-858, in ROS-GC1 has been mapped. The location and properties of this site are unique. It resides within the core domain of the catalytic module and does not require the alpha-helical dimerization domain structural element (amino acids 767-811) for activating the catalytic module. Contrary to the current beliefs, the catalytic module is intrinsically active, it is directly regulated by the neurocalcin delta-modulated Ca2+ signal and is dimeric in nature. A fold recognition based model of the catalytic domain of ROS-GC1 was built, and neurocalcin delta docking simulations were carried out to define the three-dimensional features of the interacting domains of the two molecules. These findings define a new transduction model for the Ca2+ signaling of ROS-GC1.

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