Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2

Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5535-9. doi: 10.1073/pnas.92.12.5535.


One of the membrane guanylyl cyclases (GCs), RetGC, is expressed predominantly in photoreceptors. No extracellular ligand has been described for RetGC, but it is sensitive to activation by a soluble 24-kDa protein (p24) and is inhibited by Ca2+. This enzyme is, therefore, thought to play a role in resynthesizing cGMP for photoreceptor recovery or adaptation. By screening a human retinal cDNA library at low stringency with the cytoplasmic domains from four cyclases, we cloned cDNAs encoding a membrane CG that is most closely related to RetGC. We have named this GC RetGC-2, and now term the initially described RetGC RetGC-1. By in situ hybridization, mRNA encoding RetGC-2 is found only in the outer nuclear layer and inner segments of photoreceptor cells. By using synthetic peptide antiserum specific for each RetGC subtype, RetGC-2 can be distinguished from RetGC-1 as a slightly smaller protein in immunoblots of bovine rod outer segments. Membrane GC activity of recombinant RetGC-2 expressed in human embryonic kidney 293 cells is stimulated by the activator p24 and is inhibited by Ca2+ with an EC50 value of 50-100 nM. Our data reveal a previously unappreciated diversity of photoreceptor GCs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Line
  • Cell Membrane / enzymology
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary
  • Guanylate Cyclase / genetics*
  • Guanylate Cyclase / metabolism
  • Humans
  • In Situ Hybridization
  • Macaca mulatta
  • Molecular Sequence Data
  • Photoreceptor Cells / enzymology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid


  • DNA Primers
  • DNA, Complementary
  • RNA, Messenger
  • Guanylate Cyclase

Associated data

  • GENBANK/L37378
  • GENBANK/U32856