Abstract
We have identified a novel guanylyl cyclase, named MsGC-I, that is expressed in the nervous system of Manduca sexta. MsGC-I shows highest sequence identity with receptor guanylyl cyclases throughout its catalytic and dimerization domains but does not contain the ligand-binding, transmembrane, or kinase-like domains characteristic of receptor guanylyl cyclases. In addition, MsGC-I contains a C-terminal extension of 149 amino acids that is not present in other receptor guanylyl cyclases. The sequence of MsGC-I contains no regions that show similarity to the regulatory domain of soluble guanylyl cyclases. Thus, MsGC-I appears to represent a member of a new class of guanylyl cyclases. We show that both a transcript and a protein of the sizes predicted from the MsGC-I cDNA are present in the nervous system of Manduca and that MsGC-I is expressed in a small population of neurons within the abdominal ganglia. When expressed in COS-7 cells, MsGC-I appears to exist as a soluble homodimer with high levels of basal guanylyl cyclase activity that is insensitive to stimulation by nitric oxide. Western blot analysis, however, shows that MsGC-I is localized to the particulate fraction of nervous system homogenates, suggesting that it may be membrane-associated in vivo.
Highlights
The intracellular messenger 3Ј,5Ј-cyclic guanosine monophosphate plays an important role in numerous physiological functions, including visual and chemosensory signal transduction, control of fluid and ion transport, smooth muscle relaxation, and the modulation of synaptic efficacy [1,2,3,4]
MsGC-I appears to create a new class of guanylyl cyclase, which does not fit into either the soluble or receptor guanylyl cyclase class
We do not know what this larger transcript represents. These results demonstrate that a transcript of the predicted size for MsGC-I is made within the Manduca nervous system and suggest that MsGC-I is not a truncated version of a larger receptor guanylyl cyclase
Summary
The intracellular messenger 3Ј,5Ј-cyclic guanosine monophosphate (cGMP) plays an important role in numerous physiological functions, including visual and chemosensory signal transduction, control of fluid and ion transport, smooth muscle relaxation, and the modulation of synaptic efficacy [1,2,3,4]. From DNA sequence analysis, this clone appears to contain the kinase-like, dimerization and catalytic domains characteristic of receptor guanylyl cyclases but contains no ligand-binding or transmembrane domains. This indicates that ksGC is a cytoplasmically localized guanylyl cyclase that is insensitive to NO. These sequencebased predictions have not yet been tested, as the putative protein encoded by this cDNA is enzymatically inactive when expressed in heterologous cells Another cytoplasmically localized NO-insensitive guanylyl cyclase activity has recently been reported in the nervous system of lobsters, which can be separated from a less prevalent NO sensitive form by anion exchange high performance liquid chromatography [15]
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