Olfactory marker protein interacts with adenosine nucleotide derivatives

Noriyuki Nakashima,Kie Nakashima,Akiko Nakashima,Makoto Takano

doi:10.1016/j.bbrep.2020.100887

Noriyuki Nakashima, Kie Nakashima + Show 2 more

Open Access

https://doi.org/10.1016/j.bbrep.2020.100887

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Abstract

Olfactory marker protein (OMP) is a genetic signature for mature olfactory receptor neurons (ORNs). Recently, it has been proposed that OMP directly captures odour-induced cAMP to swiftly terminate the olfactory signal transduction to maintain neuronal sensitivity. In the present study, we show that OMP can also interact with other adenosine nucleotides as ATP, ADP and AMP with different affinities. We performed bioluminescent resonant energy transfer (BRET) assay to measure the binding actions of the adenosine nucleotide derivatives in competition to cAMP. Amongst all, ATP showed the bell-shape affinity to OMP in the presence of cAMP; ADP and AMP showed fewer affinities to OMP than ATP. In the absence of cAMP analogues, ATP alone bound to OMP in a dose dependent manner with a lower affinity than to cAMP. Thus, OMP possessed different affinities to ATP in the presence or absence of cAMP. OMP may interact differentially with ATP and cAMP depending on its supply and demand along the cAMP-associated signalling in the limited spaces of cilia of ORNs.

Highlights

Olfaction starts with olfactory receptor neurons (ORNs), utilizing cAMP as a second messenger [1]
Close examinations have revealed that knocking-out of the OMP gene reduces odour discrimination ability in mice [9,10,11,12,13,14], prolongs odour response kinetics mediated by the Ca2+-permeable cyclic nucleotide-gated A2 (CNGA2) channels [15,16,17,18], and delays the Ca2+ extrusion via the Na+-Ca2+ exchanger (NCX) in ORNs [19]
We identified that ATP or ADP bound to OMP and the affinities of ATP were dependent on the presence of cAMP

Summary

Introduction

Olfaction starts with olfactory receptor neurons (ORNs), utilizing cAMP as a second messenger [1]. ORNs incessantly and resiliently utilize cAMP for responding to external stimuli. These investigations in olfaction have been facilitated by the dis covery of olfactory marker protein, (OMP), which genetically labels mature ORNs [5,6,7,8]. OMP-KO delays the maturation of axonal projections from ORNs to the olfactory bulb during development [15,20, 21], in which basal cAMP levels play a key role [17,18,22,23,24,25]

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