The Biology of Ciliary Dynamics

Hsu, Kuo-Shun; Chuang, Jen-Zen; Sung, Ching-Hwa

doi:10.1101/cshperspect.a027904

Cited by 25 publications

(32 citation statements)

References 97 publications

(114 reference statements)

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“…Active Rab7 is required for serum-induced disassembly of primary cilia Cilia dynamics reflect the equilibrium between cilia assembly and disassembly (Marshall and Rosenbaum, 2001;Liang et al, 2016;Hsu et al, 2017). It has been shown experimentally that serum starvation of cells induces cilia assembly, while culture in serum-containing medium induces cilia disassembly ( Fig.…”

Section: Resultsmentioning

confidence: 98%

Rab7 regulates primary cilia disassembly through cilia excision

Wang

Chang

et al. 2019

Journal of Cell Biology

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The primary cilium is a sensory organelle that protrudes from the cell surface. Primary cilia undergo dynamic transitions between assembly and disassembly to exert their function in cell signaling. In this study, we identify the small GTPase Rab7 as a novel regulator of cilia disassembly. Depletion of Rab7 potently induced spontaneous ciliogenesis in proliferating cells and promoted cilia elongation during quiescence. Moreover, Rab7 performs an essential role in cilia disassembly; knockdown of Rab7 blocked serum-induced ciliary resorption, and active Rab7 was required for this process. Further, we demonstrate that Rab7 depletion significantly suppresses cilia tip excision, referred to as cilia ectocytosis, which has been identified as required for cilia disassembly. Mechanically, the failure of F-actin polymerization at the site of excision of cilia tips caused suppression of cilia ectocytosis on Rab7 depletion. Overall, our results suggest a novel function for Rab7 in regulating cilia ectocytosis and cilia disassembly via control of intraciliary F-actin polymerization.

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Section: Resultsmentioning

confidence: 98%

Rab7 regulates primary cilia disassembly through cilia excision

Wang

Chang

et al. 2019

Journal of Cell Biology

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“…to interfere with PKA activity inside cilia (Mick et al, 2015). Cilia length is an important parameter that determines cilia function (Hsu, Chuang et al, 2017). However, the spatial contribution of signaling pathways in the cilium or cell body that regulate cilia length is not well understood.…”

Section: Discussionmentioning

confidence: 99%

Nanobody-directed targeting of optogenetic tools to study signaling in the primary cilium

Hansen

Kaiser

Klausen

et al. 2020

Preprint

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Compartmentalization of cellular signaling forms the molecular basis of cellular behavior. Primary cilia constitute a subcellular compartment that orchestrates signal transduction independent from the cell body. Ciliary dysfunction causes severe diseases, termed ciliopathies. Analyzing ciliary signaling and function has been challenging due to the lack of tools to manipulate and analyze ciliary signaling in living cells. Here, we describe a nanobodybased targeting approach for optogenetic tools that allows to specifically analyze ciliary signaling and function, and that is applicable in vitro and in vivo. We overcome the loss of protein function observed after direct fusion to a ciliary targeting sequence, and functionally localize the photo-activated adenylate cyclase bPAC, the light-activated phosphodiesterase LAPD, and the cAMP biosensor mlCNBD-FRET to the cilium. Using this approach, we unravel the contribution of spatial cAMP signaling in controlling cilia length. Combining optogenetics with nanobody-based targeting will pave the way to the molecular understanding of ciliary function in health and disease.

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“…2B). The photoreceptor outer segment (a modified cilium) is completely replaced in a matter of days and hence requires continuous maintenance (Besharse and Hollyfield, 1979;Hsu et al, 2017). The integrity of the cilium, both as a structural and signaling compartment, is critical for its function (Fig.…”

Section: Cilia Maintenancementioning

confidence: 99%

Maintaining centrosomes and cilia

Werner

Pimenta-Marques

Bettencourt-Dias

2017

Journal of Cell Science

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Centrosomes and cilia are present in organisms from all branches of the eukaryotic tree of life. These structures are composed of microtubules and various other proteins, and are required for a plethora of cell processes such as structuring the cytoskeleton, sensing the environment, and motility. Deregulation of centrosome and cilium components leads to a wide range of diseases, some of which are incompatible with life. Centrosomes and cilia are thought to be very stable and can persist over long periods of time. However, these structures can disappear in certain developmental stages and diseases. Moreover, some centrosome and cilia components are quite dynamic. While a large body of knowledge has been produced regarding the biogenesis of these structures, little is known about how they are maintained. In this Review, we propose the existence of specific centrosome and cilia maintenance programs, which are regulated during development and homeostasis, and when deregulated can lead to disease.

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The Biology of Ciliary Dynamics

Cited by 25 publications

References 97 publications

Rab7 regulates primary cilia disassembly through cilia excision

Rab7 regulates primary cilia disassembly through cilia excision

Nanobody-directed targeting of optogenetic tools to study signaling in the primary cilium

Maintaining centrosomes and cilia

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