title: Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia.
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.
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, 1200 Newell Drive, PO Box 100267, Gainesville, Florida 32610, USA.
authors.forename: Corey L
authors.initials: CL
authors.lastname: Williams
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, 1200 Newell Drive, PO Box 100267, Gainesville, Florida 32610, USA.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: McIntyre
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, 109 Zina Pitcher Place, 3041 Biomedical Science Research Building (BSRB), Ann Arbor, Michigan 48109, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Norris
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-5632, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Jenkins
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, 1200 Newell Drive, PO Box 100267, Gainesville, Florida 32610, USA.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biostatistics, University of Florida, RM5225, 2004 Mowry Road, Gainesville, Florida 32611, USA.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Pei
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan, 109 Zina Pitcher Place, 3041 Biomedical Science Research Building (BSRB), Ann Arbor, Michigan 48109, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Verhey
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, 1200 Newell Drive, PO Box 100267, Gainesville, Florida 32610, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Martens
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D054468:Axoneme / Q000378:metabolism* / Q000648:ultrastructure; D001692:Biological Transport; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D005407:Flagella / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D016547:Kinesins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D000097573:Red Fluorescent Protein; C506281:BBS4 protein, mouse; C506280:Bbs1 protein, mouse; C528012:Bbs2 protein, mouse; C409642:KIF17 protein, mouse