Oxygen-sensitive guanylyl cyclases in insects and their potential roles in oxygen detection and in feeding behaviors

Responses to hypoxia and hyperoxia depend critically on the ability of the animal to detect changes in O 2 levels. However, it has only been recently that an O 2-sensing system has been identified in invertebrates. Evidence is accumulating that this molecular O 2 sensor is, surprisingly, a class of soluble guanylyl cyclase (sGC) known as atypical sGCs. It has long been known that the conventional sGC α and β subunits form heterodimeric enzymes that are potently activated by NO, but do not bind O 2. By contrast, the Drosophila melanogaster atypical sGC subunits, Gyc-88E, Gyc-89Da and Gyc-89Db, are only slightly sensitive to NO, but are potently activated under hypoxic conditions. Here we review evidence that suggests that the atypical sGCs can function as molecular O 2 sensors mediating behavioral responses to hypoxia. Sequence comparisons of other predicted O 2-sensitive sGCs suggest that most, if not all, insects express two heterodimeric sGCs; an NO-sensitive isoform and a separate O 2-sensitive isoform. Expression data and recent experiments that block the function of cells that express the atypical sGCs and experiments that reduce the cGMP levels in these cells also suggest a role in behavioral responses to sweet tastants.