Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia

Corey L. Williams, Jeremy C. McIntyre, Stephen R. Norris, Paul M. Jenkins, Lian Zhang, Qinglin Pei, Kristen Verhey and Jeffrey R. Martens ()
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Corey L. Williams: College of Medicine, University of Florida
Jeremy C. McIntyre: College of Medicine, University of Florida
Stephen R. Norris: University of Michigan
Paul M. Jenkins: University of Michigan Medical School
Lian Zhang: College of Medicine, University of Florida
Qinglin Pei: University of Florida
Kristen Verhey: University of Michigan
Jeffrey R. Martens: College of Medicine, University of Florida

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Cilia dysfunction underlies a class of human diseases with variable penetrance in different organ systems. Across eukaryotes, intraflagellar transport (IFT) facilitates cilia biogenesis and cargo trafficking, but our understanding of mammalian IFT is insufficient. Here we perform live analysis of cilia ultrastructure, composition and cargo transport in native mammalian tissue using olfactory sensory neurons. Proximal and distal axonemes of these neurons show no bias towards IFT kinesin-2 choice, and Kif17 homodimer is dispensable for distal segment IFT. We identify Bardet–Biedl syndrome proteins (BBSome) as bona fide constituents of IFT in olfactory sensory neurons, and show that they exist in 1:1 stoichiometry with IFT particles. Conversely, subpopulations of peripheral membrane proteins, as well as transmembrane olfactory signalling pathway components, are capable of IFT but with significantly less frequency and/or duration. Our results yield a model for IFT and cargo trafficking in native mammalian cilia and may explain the penetrance of specific ciliopathy phenotypes in olfactory neurons.

Date: 2014
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DOI: 10.1038/ncomms6813

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