A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.
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.
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Carolina
C
Gomez-Diaz
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Benoîte
B
Bargeton
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Liliane
L
Abuin
Centre for Self-Assembled Chemical Structures (CSACS), McGill University, Montreal, Quebec, Canada H3A 2K6.|Département de Chimie, Université de Montréal, Montreal, Quebec, Canada H3C 3J7.
Natalia
N
Bukar
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Jaime H
JH
Reina
BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
Tudor
T
Bartoi
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Marion
M
Graf
Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada H3C 3J7.
Huy
H
Ong
BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.|Department of Nephrology, University of Freiburg Medical Center, 79106 Freiburg, Germany.
Maximilian H
MH
Ulbrich
Centre for Self-Assembled Chemical Structures (CSACS), McGill University, Montreal, Quebec, Canada H3A 2K6.|Département de Chimie, Université de Montréal, Montreal, Quebec, Canada H3C 3J7.
Jean-Francois
JF
Masson
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Richard
R
Benton
D000818:Animals; D030801:Animals, Genetically Modified; D018955:CD36 Antigens / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D004220:Disulfides / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D019143:Evolution, Molecular; D006031:Glycosylation; D008958:Models, Molecular; D010675:Pheromones / Q000378:metabolism*; D000072417:Protein Domains; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D043563:Receptors, Pheromone; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
D018955:CD36 Antigens; D004220:Disulfides; D029721:Drosophila Proteins; D010675:Pheromones; D011956:Receptors, Cell Surface; D043563:Receptors, Pheromone; C524729:Snmp1 protein, Drosophila