Molecular cloning of a retina-specific membrane guanylyl cyclase

115

110

Atmospheric CO2 is an important environmental cue that regulates several types of animal behavior. In mice, CO 2 responses of the olfactory sensory neurons (OSNs) require the activity of carbonic anhydrase to catalyze the conversion of CO 2 to bicarbonate and the opening of cGMP-sensitive ion channels. However, it remains unknown how the enhancement of bicarbonate levels results in cGMP production. Here, we show that bicarbonate activates cGMP-producing ability of guanylyl cyclase-D (GC-D), a membrane GC exclusively expressed in the CO 2-responsive OSNs, by directly acting on the intracellular cyclase domain of GC-D. Also, the molecular mechanism for GC-D activation is distinct from the commonly believed model of ''release from repression'' for other membrane GCs. Our results contribute to our understanding of the molecular mechanisms of CO 2 sensing and suggest diverse mechanisms of molecular activation among membrane GCs.carbonic anhydrase ͉ CNG channels ͉ necklace glomeruli ͉ transduction

Section: Resultssupporting

confidence: 54%

Guanylyl cyclase-D in the olfactory CO ₂ neurons is activated by bicarbonate

Sun

Wang

Jian

et al. 2009

115

110

“…Guanylyl cyclase [GTP pyrophosphate-Jyase (cyclizing), EC 4.6.1.2] membrane receptors appear to compose a relatively small family of proteins with a similar topographic domain structure; a single membrane-spanning domain separates an extracellular ligand-binding domain from two intracellular signature domains, a protein kinase-like and cyclase catalytic domain (10)(11)(12)(13)(14)(15)(16)(17). Guanylyl cyclases A and B (GC-A and GC-B) are members of the natriuretic peptide receptor family (10)(11)(12)(13), and guanylyl cyclase C (GC-C) encodes a heat-stable enterotoxin/guanylin peptide receptor (14,15).…”

mentioning

confidence: 99%

A receptor guanylyl cyclase expressed specifically in olfactory sensory neurons.

Fülle

Vassar

Foster

et al. 1995

255

192

“…Given that hemolymph EH concentrations are not expected to reach such high levels under physiological conditions, this raises questions regarding the function of BdmGC-1〉. Several reports indicate that some receptor GCs such as GC-E and GC-F, when expressed heterologously, generate high basal levels of cGMP (28,29). However, these cyclases are tightly regulated in the presence of GC-activating proteins (GCAPs) (30)(31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Receptor guanylyl cyclases in Inka cells targeted by eclosion hormone

Chang

Yang

Adams

et al. 2009

A signature of eclosion hormone (EH) action in insect ecdysis is elevation of cGMP in Inka cells, leading to massive release of ecdysis triggering hormone (ETH) and ecdysis initiation. Although this aspect of EH-induced signal transduction is well known, the receptor mediating this process has not been identified. Here, we describe a receptor guanylyl cyclase BdmGC-1 and its isoform BdmGC-1B in the Oriental fruit fly Bactrocera dorsalis that are activated by EH. The B form exhibits the conserved domains and putative N-glycosylation sites found in BdmGC-1, but possesses an additional 46-amino acid insertion in the extracellular domain and lacks the C-terminal tail of BdmGC-1. Combined immunolabeling and in situ hybridization reveal that BdmGC-1 is expressed in Inka cells. Heterologous expression of BdmGC-1 in HEK cells leads to robust increases in cGMP following exposure to low picomolar concentrations of EH. The B-isoform responds only to higher EH concentrations, suggesting different physiological roles of these cyclases. We propose that BdmGC-1 and BdmGC-1〉 are high-and low-affinity EH receptors, respectively.