Phosphorylation of Adenylyl Cyclase III at Serine¹⁰⁷⁶Does Not Attenuate Olfactory Response in Mice

Abstract

Feedback inhibition of adenylyl cyclase III (ACIII) via Ca2+-induced phosphorylation has long been hypothesized to contribute to response termination and adaptation of olfactory sensory neurons (OSNs). To directly determine the functional significance of this feedback mechanism for olfaction in vivo, we genetically mutated serine1076 of ACIII, the only residue responsible for Ca2+-induced phosphorylation and inhibition of ACIII (Wei et al., 1996; Wei et al., 1998), to alanine in mice. Immunohistochemistry and Western blot analysis showed that the mutation affects neither the cilial localization nor the expression level of ACIII in OSNs. Electroolfactogram analysis showed no differences in the responses between wildtype and mutant mice to single-pulse odorant stimulations or in several stimulation paradigms for adaptation. These results suggest that phosphorylation of ACIII on serine1076 plays a far less important role in olfactory response attenuation than previously thought.

Distinct signaling of Drosophila chemoreceptors in olfactory sensory neurons

“…In vertebrate OSNs, several mechanisms have been proposed, including the desensitization of transduction channels, phosphorylation of odorant receptors, inhibition of adenylyl cyclase, and potentiation of phosphodiesterase activity (37,38,45). Recent molecular genetic studies have revealed, however, that adaptation in vertebrate OSNs is more complex than previously understood (46,47). To date, the odor transduction mechanism in Drosophila OSNs remains unclear, although heterologous studies have suggested novel and controversial mechanisms (43).…”

Tracking of unfamiliar odors is facilitated by signal amplification through anoctamin 2 chloride channels in mouse olfactory receptor neurons

“…; Cygnar et al. ; Stephan et al. ), a concern that may also apply to peripheral signal amplification.…”

“…While the precise relation between single-ORN recordings and EOGs was, to our knowledge, never explored systematically, there are examples that the two methods may support inconsistent concepts. Particularly for complex transduction processes like adaptation, single-ORN recordings offer only limited value for predicting the compound afferent signal and its central processing (Song et al 2008;Cygnar et al 2012;Stephan et al 2012), a concern that may also apply to peripheral signal amplification. Isolated ORNs certainly offer better access to dissecting individual aspects of the transduction process, but EOG recordings are better suited for the study of afferent signals.…”

From the Cover: Cadmium Exposure Differentially Alters Odorant-Driven Behaviors and Expression of Olfactory Receptors in Juvenile Coho Salmon(Oncorhynchus kisutch)

“…Deactivation of ACIII, following activation by ORs, may rely on calcium signaling via activation of CaMKII, which Cd has been shown to directly activate (Wei et al, 1998). However, this deactivation pathway for ACIII is still under debate (Cygnar et al, 2012).…”