A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease

Abstract

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings.

FIGURE 1

Proposed scavenger receptor nomenclature formula. SR stands for scavenger receptor. SR is followed by a hyphen, then a capital letter represents the class of scavenger receptor (A–J), followed by an Arabic numeral representing the type of molecule within the class (the numbering is based on the order in which the molecules were identified). Alternatively spliced forms of a molecule will be designated as 1.1, 1.2, etc. For existing spliced variants, the longest variant in terms of amino acid sequence will be given the first number.

FIGURE 2

Schematic representation of different classes of scavenger receptors. Mammalian scavenger receptors are divided into 12 classes. The various protein or carbohydrate domains are identified in the key within the figure. Class C is not represented here because it is present only in Drosophila melanogaster.