Ca2+ Sensor GCAP1: A Constitutive Element of the ONE-GC-Modulated Odorant Signal Transduction Pathway

In a small subset of the olfactory sensory neurons, the odorant receptor ONE-GC guanylate cyclase is a central transduction component of the cyclic G MP signaling pathway. In a two-step transduction model, the odorant, uroguanylin, binds to the extracellular domain and activates its intracellular domain to generate the odorant second messenger, cyclic GM P. This study via comprehensive technology, including gene deletion, live cell Forster resonance energy transfer (FRET), and surface plasmon resonance (SPR) spectroscopy, documents the identity ()la remarkably intriguing operation of a Ca2+ sensor component (tithe ONE-GC transduction machinery, GCAP I. In the ciliary membranes, the sites of odorant transduction, GCAP1 is biochemically and physiologically coupled to ONE-GC. Strikingly, this coupling reverses its well-established function in ROS-GCI signaling, linked with phototransduction. In response to the free Ca2+ range from nanomolar to semimicromolar, it inhibits ROS-GCI, yet in this range, it incrementally stimulates ONE-GC. These two opposite modes of signaling two SENSORY processes by a single Ca2+ sensor define a new transduction paradigm of membrane guanylate cyclases. This paradigm is pictorially presented.