Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors
Jing Wang,
Neelima Vaddadi,
Joseph S. Pak,
Yeonwoo Park,
Sabrina Quilez,
Christina A. Roman,
Emilie Dumontier,
Joseph W. Thornton,
Jean-François Cloutier,
Engin Özkan
Affiliations
Jing Wang
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA; Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL 60637, USA
Neelima Vaddadi
The Neuro–Montreal Neurological Institute and Hospital, McGill University, Montréal, QC H3A 2B4, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada
Joseph S. Pak
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA; Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL 60637, USA
Yeonwoo Park
Committee on Genetics, Genomics and Systems Biology, The University of Chicago, Chicago, IL 60637, USA
Sabrina Quilez
The Neuro–Montreal Neurological Institute and Hospital, McGill University, Montréal, QC H3A 2B4, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada
Christina A. Roman
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA
Emilie Dumontier
The Neuro–Montreal Neurological Institute and Hospital, McGill University, Montréal, QC H3A 2B4, Canada
Joseph W. Thornton
Committee on Genetics, Genomics and Systems Biology, The University of Chicago, Chicago, IL 60637, USA; Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA; Department of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, USA
Jean-François Cloutier
The Neuro–Montreal Neurological Institute and Hospital, McGill University, Montréal, QC H3A 2B4, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada; Department of Anatomy and Cell Biology, McGill University, Montréal, QC H3A 0C7, Canada; Corresponding author
Engin Özkan
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA; Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL 60637, USA; Corresponding author
Summary: Projections from sensory neurons of olfactory systems coalesce into glomeruli in the brain. The Kirrel receptors are believed to homodimerize via their ectodomains and help separate sensory neuron axons into Kirrel2- or Kirrel3-expressing glomeruli. Here, we present the crystal structures of homodimeric Kirrel receptors and show that the closely related Kirrel2 and Kirrel3 have evolved specific sets of polar and hydrophobic interactions, respectively, disallowing heterodimerization while preserving homodimerization, likely resulting in proper segregation and coalescence of Kirrel-expressing axons into glomeruli. We show that the dimerization interface at the N-terminal immunoglobulin (IG) domains is necessary and sufficient to create homodimers and fail to find evidence for a secondary interaction site in Kirrel ectodomains. Furthermore, we show that abolishing dimerization of Kirrel3 in vivo leads to improper formation of glomeruli in the mouse accessory olfactory bulb as observed in Kirrel3−/− animals. Our results provide evidence for Kirrel3 homodimerization controlling axonal coalescence.
