# Renaming the ‘OS-D/CSP’ Family (Part 1): ‘4-Cysteine Soluble Proteins’ (4CSPs)—Molecular Nomenclature, Structure, Expression, Evolution, Tissue-Distribution, and Pleiotropy

## TL;DR

This paper proposes renaming the 'OS-D/CSP' protein family to '4-Cysteine Soluble Proteins' (4CSPs) to better reflect their molecular features and diverse functions beyond chemosensation.

## Contribution

The paper introduces a new nomenclature for a protein family based on conserved cysteine residues and broader functional roles beyond olfaction.

## Key findings

- 4CSPs are expressed in multiple tissues beyond sensory organs, indicating pleiotropic roles.
- The name '4Cysteine Soluble Protein' better reflects the conserved four cysteine residues and diverse functions.
- Evidence supports renaming CSPs to 4CSPs due to outdated nomenclature and new functional insights.

## Abstract

<<Chemosensory proteins (CSPs) are small soluble proteins that mediate olfactory recognition at the periphery of sensory receptors in insects, similarly to odorant-binding proteins (OBPs)>>?. We argue that the nomenclature of this insect protein superfamily is outdated (it is based on early studies on its presence in the aqueous lymph of antennal sensilla). However, given the collective sum of research conducted on this topic over the past 20 years, the new name for the protein molecule superfamily needs to be far more accurate. We suggest changing the name of this protein family to reflect the most recent findings about its locations, roles, and characteristics. We suggest changing the protein’s name from “CSP” to “4CSP” (4-Cysteine Soluble Protein) due to the highly conserved molecular feature of its four neighboring cysteine residues. Then, we suggest using the common peptide five-letter code (“Bommo-4CSP”) for abbreviations of other insect, crustacean, and bacterial proteins.

Chemosensory proteins (CSPs) are found in the olfactory sensory organs (antennae and maxillary palps) and/or gustatory sensory organs (labellum and legs) and have long been accepted to function through the binding of odorants. However, the same CSPs are also expressed in many tissues other than olfactory and gustatory organs, such as the gut, brain, fat body, wing, epidermis, Corpora allata, salivary gland, pheromone gland, prothoracic gland, etc. In this report, we suggest renaming the “chemosensory protein (CSP)” the “4-Cysteine Soluble Protein (4CSP)”. This paradigm and nomenclature shift is based on molecular characteristics, genomic mining, tissue distribution, and functional roles beyond those related to olfaction. We examined prior studies on this protein gene family to bolster the renaming, highlighting the most recent findings that we ascribe to “pleiotropic properties” and evolutionary relevance rather than smell. The scope of the report, per se, is broad, and this is especially true given the volume of data that has been gathered on 4CSP expressed in ways that are not consistent with the olfactory paradigm. Statements outlining the many chemosensory properties of 4CSPs, particularly how they activate olfactory receptor neurons (ORNs), are currently scarce, if they exist at all. Many debates currently focus on 4CSPs’ non-chemosensory functions, which are backed by a multitude of evidence, from gene evolution to tissue distribution. Therefore, strong arguments in favor of renaming chemosensory proteins are becoming evident here, outweighing the drawbacks.