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Hedgehog signaling regulates ciliary localization of mouse odorant receptors
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0000-0001-6052-4314
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
2017 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 44, p. E9386-E9394Article in journal (Refereed) Published
Abstract [en]

The ciliary localization of odorant receptors (ORs) is evolutionary conserved and essential for olfactory transduction. However, how the transport of ORs is regulated in mammalian olfactory sensory neurons is poorly understood. Here we demonstrate that odorant responsiveness and OR transport is regulated by the Hedgehog pathway. OR transport is inhibited by conditional gene inactivation of the Hedgehog signal mediator Smoothened (Smo) as well as by systemic administration of the Smo inhibitor vismodegib, a clinically used anticancer drug reported to distort smell perception in patients. The ciliary phenotype of Smo inhibition is haploinsufficient, cell autonomous, and correlates with the accumulation of OR-containing putative transport vesicles in the cytosol. The Smo-dependent OR transport route works in parallel with a low basal transport of vesicle containing both ORs and other olfactory transduction components. These findings both define a physio logical function of Hedgehog signaling in olfaction and provide an important evolutionary link between olfaction and the requirement of a ciliary compartment for Hedgehog signaling.

Place, publisher, year, edition, pages
National Academy of Sciences , 2017. Vol. 114, no 44, p. E9386-E9394
Keywords [en]
odorant receptors, Hedgehog pathway, Smoothened, vismodegib, cilia transport
National Category
Genetics
Identifiers
URN: urn:nbn:se:umu:diva-141992DOI: 10.1073/pnas.1708321114ISI: 000414127400026PubMedID: 29078327OAI: oai:DiVA.org:umu-141992DiVA, id: diva2:1159429
Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2018-06-09Bibliographically approved

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Maurya, Devendra KumarBohm, StaffanAlenius, Mattias

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Maurya, Devendra KumarBohm, StaffanAlenius, Mattias
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CiteExportLink to record
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