A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism

Nat Commun. 2016 Jun 15;7:11866. doi: 10.1038/ncomms11866.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • CD36 Antigens / chemistry*
  • CD36 Antigens / metabolism*
  • Conserved Sequence / genetics
  • Disulfides / metabolism
  • Drosophila / metabolism*
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / metabolism*
  • Evolution, Molecular
  • Glycosylation
  • Models, Molecular
  • Pheromones / metabolism*
  • Protein Domains
  • Protein Transport
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Pheromone
  • Structural Homology, Protein
  • Structure-Activity Relationship

Substances

  • CD36 Antigens
  • Disulfides
  • Drosophila Proteins
  • Pheromones
  • Receptors, Cell Surface
  • Receptors, Pheromone
  • Snmp1 protein, Drosophila