1. A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.
- Author
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Gomez-Diaz C, Bargeton B, Abuin L, Bukar N, Reina JH, Bartoi T, Graf M, Ong H, Ulbrich MH, Masson JF, and Benton R
- Subjects
- Animals, Animals, Genetically Modified, Conserved Sequence genetics, Disulfides metabolism, Evolution, Molecular, Glycosylation, Models, Molecular, Protein Domains, Protein Transport, Receptors, Pheromone, Structural Homology, Protein, Structure-Activity Relationship, CD36 Antigens chemistry, CD36 Antigens metabolism, Drosophila metabolism, Drosophila Proteins chemistry, Drosophila Proteins metabolism, Pheromones metabolism, Receptors, Cell Surface chemistry, Receptors, Cell Surface metabolism
- Abstract
CD36 transmembrane proteins have diverse roles in lipid uptake, cell adhesion and pathogen sensing. Despite numerous in vitro studies, how they act in native cellular contexts is poorly understood. A Drosophila CD36 homologue, sensory neuron membrane protein 1 (SNMP1), was previously shown to facilitate detection of lipid-derived pheromones by their cognate receptors in olfactory cilia. Here we investigate how SNMP1 functions in vivo. Structure-activity dissection demonstrates that SNMP1's ectodomain is essential, but intracellular and transmembrane domains dispensable, for cilia localization and pheromone-evoked responses. SNMP1 can be substituted by mammalian CD36, whose ectodomain can interact with insect pheromones. Homology modelling, using the mammalian LIMP-2 structure as template, reveals a putative tunnel in the SNMP1 ectodomain that is sufficiently large to accommodate pheromone molecules. Amino-acid substitutions predicted to block this tunnel diminish pheromone sensitivity. We propose a model in which SNMP1 funnels hydrophobic pheromones from the extracellular fluid to integral membrane receptors.
- Published
- 2016
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