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ArticleHigh density and ligand affinity confer ultrasensitive signal detection by a guanylyl cyclase chemoreceptor(Rockefeller University Press, 2014-08-18) Pichlo, Magdalena ; Bungert-Plumke, Stefanie ; Weyand, Ingo ; Seifert, Reinhard ; Bonigk, Wolfgang ; Strunker, Timo ; Kashikar, Nachiket D. ; Goodwin, Normann ; Muller, Astrid ; Pelzer, Patric ; Van, Qui ; Enderlein, Jorg ; Klemm, Clementine ; Krause, Eberhard ; Trotschel, Christian ; Poetsch, Ansgar ; Kremmer, Elisabeth ; Kaupp, U. BenjaminGuanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3′,5′-monophosphate, control several sensory functions, such as phototransduction, chemosensation, and thermosensation, in many species from worms to mammals. The GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations with single-molecule sensitivity. The molecular and cellular underpinnings of such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this paper, we show that an exquisitely high density of 3 × 105 GC chemoreceptors and subnanomolar ligand affinity provide a high ligand-capture efficacy and render sperm perfect absorbers. The GC activity is terminated within 150 ms by dephosphorylation steps of the receptor, which provides a means for precise control of the GC lifetime and which reduces “molecule noise.” Compared with other ultrasensitive sensory systems, the 10-fold signal amplification by the GC receptor is surprisingly low. The hallmarks of this signaling mechanism provide a blueprint for chemical sensing in small compartments, such as olfactory cilia, insect antennae, or even synaptic boutons.