Differential activation of rod outer segment membrane guanylate cyclases, ROS-GC1 and ROS-GC2, by CD-GCAP and identification of the signaling domain

Biochemical and Biophysical Research Communications
T DudaR K Sharma

Abstract

The ROS-GC is one of the two subfamilies of membrane guanylate cyclases. It distinguishes itself from the other surface receptor subfamily in that its members are not regulated by extracellular peptides; instead, they are modulated by intracellular Ca2+ signals. There are two members of the subfamily, ROS-GC1 and ROS-GC2. An intriguing feature of ROS-GC1 is that it has two Ca2+ switches. One switch inhibits the enzyme at micromolar concentrations of Ca2+, and the other stimulates. The inhibitory switch is linked to phototransduction, and it is likely that the stimulatory switch is linked to retinal synaptic activity. Ca2+ acts indirectly via Ca(2+)-binding proteins, GCAPs and CD-GCAP. GCAPs modulate the inhibitory switching component of the cyclase and CD-GCAP turns on the activation signaling switch. The activating switch of ROS-GC2 has not so far been scrutinized. The present study shows that CD-GCAP is linked to the activation signaling switch of ROS-GC2, but the linkage is about 10-fold weaker than that of the ROS-GC1. Thus, CD-GCAP is a specific ROS-GC1 activator. Furthermore, through a series of expression studies on the mutants involving deletion, building of hybrids, and reconstruction of a heterologous cyclase, the stu...Continue Reading

References

Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·D G LoweJ B Hurley
Jan 17, 1995·Proceedings of the National Academy of Sciences of the United States of America·R B YangH J Fülle
May 17, 1996·The Journal of Biological Chemistry·R P LauraJ B Hurley
Jul 2, 1996·Biochemistry·T DudaR K Sharma

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Citations

Apr 18, 2012·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Xiao-Hong WenRameshwar K Sharma
Apr 12, 2014·Frontiers in Molecular Neuroscience·Rameshwar K SharmaTeresa Duda
May 21, 1999·The Journal of Biological Chemistry·H YuA Yamazaki
Dec 3, 2009·Molecular and Cellular Biochemistry·Rameshwar K Sharma, Teresa Duda
Dec 4, 2009·Molecular and Cellular Biochemistry·Rameshwar K Sharma
May 8, 1998·Biochemical and Biophysical Research Communications·R M GoraczniakR K Sharma

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