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Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia
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Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia
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Journal Article
Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia
2014
Overview
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.
Loss of olfactory function is one of the many symptoms of the ciliopathy Bardet–Biedl syndrome. Williams
et al
. show that Bardet–Biedl proteins are components of intraflagellar transport particles within cilia, and directly visualize their trafficking in native mammalian olfactory neurons.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
Subject
/ 14
/ 14/19
/ 14/35
/ 14/63
/ 42/44
/ 64/60
/ 82/80
/ Animals
/ Green Fluorescent Proteins - genetics
/ Green Fluorescent Proteins - metabolism
/ Humanities and Social Sciences
/ Luminescent Proteins - genetics
/ Luminescent Proteins - metabolism
/ Mammals
/ Mice
/ Microtubule-Associated Proteins - genetics
/ Microtubule-Associated Proteins - metabolism
/ Olfactory Receptor Neurons - metabolism
/ Olfactory Receptor Neurons - ultrastructure
/ Recombinant Fusion Proteins - genetics
/ Recombinant Fusion Proteins - metabolism
/ Science
