UMMS Affiliation

Program in Molecular Medicine

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Biochemistry | Cell Biology | Developmental Biology | Enzymes and Coenzymes


The Hedgehog pathway, critical to vertebrate development, is organized in primary cilia. Activation of signaling causes the Hedgehog receptor Ptch1 to exit cilia, allowing a second receptor, Smo, to accumulate in cilia and activate the downstream steps of the pathway. Mechanisms regulating the dynamics of these receptors are unknown, but the ubiquitination of Smo regulates its interaction with the intraflagellar transport system to control ciliary levels. A focused screen of ubiquitin-related genes identified nine required for maintaining low ciliary Smo at the basal state. These included cytoplasmic E3s (Arih2, Mgrn1, and Maea), a ciliary localized E3 (Wwp1), a ciliary localized E2 (Ube2l3), a deubiquitinase (Bap1), and three adaptors (Kctd5, Skp1a, and Skp2). The ciliary E3, Wwp1, binds Ptch1 and localizes to cilia at the basal state. Activation of signaling removes both Ptch1 and Wwp1 from cilia, thus providing an elegant mechanism for Ptch1 to regulate ciliary Smo levels.


Biochemistry, Cell signaling, Cilia, Development

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Copyright © 2021 Lv et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at

DOI of Published Version



Lv B, Stuck MW, Desai PB, Cabrera OA, Pazour GJ. E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened. J Cell Biol. 2021 Sep 6;220(9):e202010177. doi: 10.1083/jcb.202010177. Epub 2021 Jun 23. PMID: 34161574; PMCID: PMC8236919. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of cell biology

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Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.