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Guanylyl Cyclase-D in the Olfactory C0₂ Neurons Is Activated by Bicarbonate

Liming Sun, Huayi Wang, Ji Hu, Jinlong Han, Hiroaki Matsunami, Minmin Luo and Xiaodong Wang
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 6 (Feb. 10, 2009), pp. 2041-2046
Stable URL: http://www.jstor.org/stable/40421719
Page Count: 6
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Abstract

Atmospheric CO₂ is an important environmental cue that regulates several types of animal behavior. In mice, CO₂ responses of the olfactory sensory neurons (OSNs) require the activity of carbonic anhydrase to catalyze the conversion of CO₂ 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 CO₂-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 CO₂ sensing and suggest diverse mechanisms of molecular activation among membrane GCs.

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