Presentation Details
An enhanced evolutionary capacitance enables the functional expression of odorant receptors with cryptic mutations

Claire March1, Kentaro Ikegami 1, 2, Maira H.Nagai 1, Soumadwip Ghosh 3, Matthew Do 1, Ruchira Sharma 1, Elise S.Bruguera1, Yueyang Eric Lu 1, Yosuke Fukutani 1, 2, Nagarajan Vaidehi 3, Masafumi Yohda2, Hiroaki Matsunami 1.

1Duke University, Durham, NC, USA.2Tokyo University of Agriculture and Technology, Tokyo, Japan.3Beckman Research Institute of the City of Hope, Duarte, CA, USA


Odor detection begins with odorant receptors (OR), which belong to the large family of rhodopsin-like G protein-coupled receptors. In order to discriminate the vast number of volatile chemicals, the ORs repertoire gained a high functional diversity by rapidly evolving, becoming the largest sub-family of G protein-coupled receptors. The mechanism allowing this rapid evolution while conserving the functionality of the ORs remains unknown. Here, we sought to understand at a molecular level the ORs properties underlying their functional expression in olfactory sensory neurons while they remain poorly expressed in heterologous cells. Using a combination of in silico and in vitro tools, we demonstrate that the divergences from the conserved residues in this family are cryptic mutations that increase OR repertoire diversity at the expense of functionality. The divergence from conserved residues destabilizes the structure of the OR to decrease its cell surface expression in heterologous cells. The receptor transporting proteins RTP1 and RTP2 compensate this structural destabilization by promoting most ORs transport from the endoplasmic reticulum to the cell surface allowing their functional expression. We hypothesis that olfactory-specific evolutionary capacitors, such as RTP1, RTP2, and other contributors yet to be discovered, enables ORs functional cell surface expression, supporting the rapid evolution of ORs to facilitate sensory adaptation.

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