Receptor guanylyl cyclase‐ G is a novel thermosensory protein activated by cool temperatures

Transmembrane guanylyl cyclases ( GC s), with activity regulated by peptide ligands and/or calcium‐binding proteins, are essential for various physiological and sensory processes. The mode of activation of the GC subtype GC ‐G, which is expressed in neurons of the G rueneberg ganglion that respond to cool temperatures, has been elusive. In searching for appropriate stimuli to activate GC ‐G, we found that its enzymatic activity is directly stimulated by cool temperatures. In this context, it was observed that dimerization/oligomerization of GC ‐G, a process generally considered as critical for enzymatic activity of GC s, is strongly enhanced by coolness. Moreover, heterologous expression of GC ‐G in cultured cells rendered these cells responsive to coolness; thus, the protein might be a sensor for cool temperatures. This concept is supported by the observation of substantially reduced coolness‐induced response of G rueneberg ganglion neurons and coolness‐evoked ultrasonic vocalization in GC ‐G‐deficient mouse pups. GC ‐G may be a novel thermosensory protein with functional implications for the G rueneberg ganglion, a sensory organ responding to cool temperatures.