BBS4 is required for intraflagellar transport coordination and basal body number in mammalian olfactory cilia

Cedric R Uytingco; Corey L Williams; Chao Xie; Dana T Shively; Warren W Green; Kirill Ukhanov; Lian Zhang; Darryl Y Nishimura; Val C Sheffield; Jeffrey R Martens

doi:10.1242/jcs.222331

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BBS4 is required for intraflagellar transport coordination and basal body number in mammalian olfactory cilia

Journal article

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BBS4 is required for intraflagellar transport coordination and basal body number in mammalian olfactory cilia

Cedric R Uytingco, Corey L Williams, Chao Xie, Dana T Shively, Warren W Green, Kirill Ukhanov, Lian Zhang, Darryl Y Nishimura, Val C Sheffield and Jeffrey R Martens

Journal of cell science, Vol.132(5), p.jcs222331

03/01/2019

DOI: 10.1242/jcs.222331

PMCID: PMC6432715

PMID: 30665891

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Abstract

Bardet–Beidl syndrome (BBS) manifests from genetic mutations encoding for one or more BBS proteins. BBS4 loss impacts olfactory ciliation and odor detection, yet the cellular mechanisms remain unclear. Here, we report that Bbs4 -/− mice exhibit shorter and fewer olfactory sensory neuron (OSN) cilia despite retaining odorant receptor localization. Within Bbs4 −/− OSN cilia, we observed asynchronous rates of IFT-A/B particle movements, indicating miscoordination in IFT complex trafficking. Within the OSN dendritic knob, the basal bodies are dynamic, with incorporation of ectopically expressed centrin-2 and γ-tubulin occurring after nascent ciliogenesis. Importantly, BBS4 loss results in the reduction of basal body numbers separate from cilia loss. Adenoviral expression of BBS4 restored OSN cilia lengths and was sufficient to re-establish odor detection, but failed to rescue ciliary and basal body numbers. Our results yield a model for the plurality of BBS4 functions in OSNs that includes intraciliary and periciliary roles that can explain the loss of cilia and penetrance of ciliopathy phenotypes in olfactory neurons. Highlighted Article: Bbs4 −/− mice exhibited reduced olfactory sensory neuron cilia length/number and basal body number, as well as miscoordination of intraflagellar transport. Ectopic re-expression of BBS4 lengthened cilia, which alone was sufficient to rescue olfactory function.

Intraflagellar transport

136

Olfactory cilia

Gene therapy

Peripheral olfactory system

Basal body

Bardet–Biedl syndrome

Details

Title: Subtitle: BBS4 is required for intraflagellar transport coordination and basal body number in mammalian olfactory cilia
Creators: Cedric R Uytingco - Center for Smell and Taste, University of Florida College of Medicine
Corey L Williams - Center for Smell and Taste, University of Florida College of Medicine
Chao Xie - Center for Smell and Taste, University of Florida College of Medicine
Dana T Shively - Center for Smell and Taste, University of Florida College of Medicine
Warren W Green - Center for Smell and Taste, University of Florida College of Medicine
Kirill Ukhanov - Center for Smell and Taste, University of Florida College of Medicine
Lian Zhang - Center for Smell and Taste, University of Florida College of Medicine
Darryl Y Nishimura - University of Iowa
Val C Sheffield - University of Iowa
Jeffrey R Martens - Center for Smell and Taste, University of Florida College of Medicine
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.132(5), p.jcs222331
Publisher: The Company of Biologists Ltd
DOI: 10.1242/jcs.222331
PMID: 30665891
PMCID: PMC6432715
ISSN: 0021-9533
eISSN: 1477-9137
Grant note: R01 EY017168 / ; R01 DC009606 / ;
Language: English
Date published: 03/01/2019
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9984070009302771

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