Deciphering the function of the CNGB1b subunit in olfactory CNG channels.

Vasilica Nache,Klaus Benndorf,Frank Schwede,Jana Kusch,Nisa Wongsamitkul,Thomas Zimmer

doi:10.1038/srep29378

Abstract

Olfactory cyclic nucleotide-gated (CNG) ion channels are key players in the signal transduction cascade of olfactory sensory neurons. The second messengers cAMP and cGMP directly activate these channels, generating a depolarizing receptor potential. Olfactory CNG channels are composed of two CNGA2 subunits and two modulatory subunits, CNGA4, and CNGB1b. So far the exact role of the modulatory subunits for channel activation is not fully understood. By measuring ligand binding and channel activation simultaneously, we show that in functional heterotetrameric channels not only the CNGA2 subunits and the CNGA4 subunit but also the CNGB1b subunit binds cyclic nucleotides and, moreover, also alone translates this signal to open the pore. In addition, we show that the CNGB1b subunit is the most sensitive subunit in a heterotetrameric channel to cyclic nucleotides and that it accelerates deactivation to a similar extent as does the CNGA4 subunit. In conclusion, the CNGB1b subunit participates in ligand-gated activation of olfactory CNG channels and, particularly, contributes to rapid termination of odorant signal in an olfactory sensory neuron.

Highlights

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels that play an important role for the sensory signaling in the vertebrate visual and olfactory system[1]
Studying ligand binding to CNGA4 and CNGB1b subunits has proven difficult because these subunits can only form functional channels when coexpressed with the CNGA2 subunit
The idea that the cyclic nucleotide-binding domain (CNBD) of CNGB1b is not involved in ligand binding is a priori not absurd because hERG channels, which play an important role in the repolarization phase of the cardiac action potential[22], are not regulated by cyclic nucleotides they contain a structurally related cyclic nucleotide-binding homology domain at their C-terminus[23,24]

Summary

Introduction

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels that play an important role for the sensory signaling in the vertebrate visual and olfactory system[1]. At the C-terminus each subunit contains a cyclic nucleotide-binding domain (CNBD)[2] Despite these structural similarities, only CNGA1, CNGA2 and CNGA3 subunits are able to form functional channels on their own when expressed heterologously, whereas the CNGB and CNGA4 subunits do not[9,10,11]. The idea that the CNBD of CNGB1b is not involved in ligand binding is a priori not absurd because hERG channels, which play an important role in the repolarization phase of the cardiac action potential[22], are not regulated by cyclic nucleotides they contain a structurally related cyclic nucleotide-binding homology domain at their C-terminus[23,24]

Methods

Results

Conclusion