BBS4 and BBS5 show functional redundancy in the BBSome to regulate the degradative sorting of ciliary sensory receptors

Qingwen Xu, Yuxia Zhang, Qing Wei, Yan Huang, Yan Li, Kun Ling, Jinghua Hu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Cilia harbor sensory receptors for various signaling cascades critical for vertebrate development. However, the mechanisms underlying the ciliary homeostasis of sensory receptors remain elusive. Here, we demonstrate that BBS<inf>-4</inf> and BBS<inf>-5</inf>, two distinct BBSome components, show unexpected functional redundancy in the context of cilia in C. elegans. BBS<inf>-4</inf> directly interacts with BBS<inf>-5</inf> and the interaction can be disrupted by a conserved mutation identified in human BBS<inf>4</inf>. Surprisingly, we found that BBS<inf>-4</inf> and BBS<inf>-5</inf> act redundantly in the BBSome to regulate the ciliary removal, rather than the ciliary entry or retrograde IFT transport, of various sensory receptors. Further analyses indicate that co-depletion of BBS<inf>-4</inf> and BBS<inf>-5</inf> disrupts the lysosome-targeted degradative sorting of ciliary sensory receptors. Moreover, mammalian BBS<inf>4</inf> and BBS<inf>5</inf> also interact directly and coordinate the ciliary removal of polycystin 2. Hence, we reveal a novel and highly conserved role for the BBSome in fine-tuning ciliary signaling by regulating the ciliary removal of sensory receptors for lysosomal degradation.

Original languageEnglish (US)
Article number11855
JournalScientific Reports
Volume5
DOIs
StatePublished - Jul 7 2015

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Sensory Receptor Cells
Cilia
Lysosomes
Vertebrates
Homeostasis
Mutation

ASJC Scopus subject areas

  • General

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BBS4 and BBS5 show functional redundancy in the BBSome to regulate the degradative sorting of ciliary sensory receptors. / Xu, Qingwen; Zhang, Yuxia; Wei, Qing; Huang, Yan; Li, Yan; Ling, Kun; Hu, Jinghua.

In: Scientific Reports, Vol. 5, 11855, 07.07.2015.

Research output: Contribution to journalArticle

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abstract = "Cilia harbor sensory receptors for various signaling cascades critical for vertebrate development. However, the mechanisms underlying the ciliary homeostasis of sensory receptors remain elusive. Here, we demonstrate that BBS-4 and BBS-5, two distinct BBSome components, show unexpected functional redundancy in the context of cilia in C. elegans. BBS-4 directly interacts with BBS-5 and the interaction can be disrupted by a conserved mutation identified in human BBS4. Surprisingly, we found that BBS-4 and BBS-5 act redundantly in the BBSome to regulate the ciliary removal, rather than the ciliary entry or retrograde IFT transport, of various sensory receptors. Further analyses indicate that co-depletion of BBS-4 and BBS-5 disrupts the lysosome-targeted degradative sorting of ciliary sensory receptors. Moreover, mammalian BBS4 and BBS5 also interact directly and coordinate the ciliary removal of polycystin 2. Hence, we reveal a novel and highly conserved role for the BBSome in fine-tuning ciliary signaling by regulating the ciliary removal of sensory receptors for lysosomal degradation.",
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