Guanylyl cyclase-D in the olfactory CO2 neurons is activated by bicarbonate.
Atmospheric CO(2) 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.
Sun
Liming
L
National Institute of Biological Sciences, Beijing 102206 China.
Wang
Huayi
H
Hu
Ji
J
Han
Jinlong
J
Matsunami
Hiroaki
H
Luo
Minmin
M
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D051379:Mice; D018034:Olfactory Receptor Neurons / Q000201:enzymology*; D011956:Receptors, Cell Surface / Q000378:metabolism*
D001639:Bicarbonates; D011956:Receptors, Cell Surface; D002245:Carbon Dioxide; D006162:Guanylate Cyclase; C484774:Gucy2d protein, mouse; D006152:Cyclic GMP