Comparative Analysis of Ciliary Membranes and Ectosomes

Long, Huan; Zhang, Fan; Xu, Nannan; Gai, Liu; Diener, Dennis R.; Rosenbaum, Joel L.; Huang, Kaiyao

doi:10.1016/j.cub.2016.09.055

Cited by 90 publications

(112 citation statements)

References 34 publications

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“…EVs are sub-micron sized membrane-enclosed packages of proteins, lipids, and nucleic acids [7] used for internal communication between distant cells [49] and external communication between conspecific animals [7]. EV shedding and release is an evolutionarily conserved function of cilia and observed in Chlamydomonas , C. elegans , and mammals [6, 7, 9–11]. Mechanisms controlling formation, shedding and release of these ciliary EVs called ectosomes are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Glutamylation Regulates Transport, Specializes Function, and Sculpts the Structure of Cilia

et al. 2017

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Summary Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a “Tubulin Code” that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of kinesin-2 OSM-3/KIF17, while a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons. Here, we examine the role of PTMs and the Tubulin Code in the cililary specialization of EV-releasing neurons using genetics, fluorescence microscopy, kymography, electron microscopy, and sensory behavioral assays. Although the C. elegans genome encodes five tubulin tyrosine ligase-like (TTLL) glutamylases, only ttll-11 specifically regulates PKD-2 localization in EV-releasing neurons. In EV-releasing cephalic male (CEM) cilia, TTLL-11 and the deglutamylase CCPP-1 regulate remodeling of 9+0 MT doublets into 18 singlet MTs. Balanced TTLL-11 and CCPP-1 activity fine-tunes glutamylation to control velocity of kinesin-2 OSM-3/KIF17 and kinesin-3 KLP-6 without affecting the IFT kinesin-II. TTLL-11 is transported by ciliary motors. TTLL-11 and CCPP-1 are also required for the ciliary function of releasing bioactive EVs, and TTLL-11 is itself a novel EV cargo. Therefore, MT glutamylation, as part of the tubulin code, controls ciliary specialization, ciliary motor-based transport, and ciliary EV release in a living animal. We suggest that cell-specific control of MT glutamylation may be a conserved mechanism to specialize the form and function of cilia.

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Section: Discussionmentioning

confidence: 99%

Glutamylation Regulates Transport, Specializes Function, and Sculpts the Structure of Cilia

et al. 2017

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“…Components of the ESRCT complex are present in cilia-derived vesicles and the topology of ectosome formation from cilia recapitulates other ESCRT-based events. 107 Vesicle formation also involves the actin-based cytoskeleton. 108,109 The role of IFT in vesicle formation is unclear but it could deliver vesicle-specific proteins to the ciliary tip.…”

Section: Ift and Ectosomes (… And The Cell Cycle)mentioning

confidence: 99%

Protein transport in growing and steady‐state cilia

Lechtreck

Weghe

Harris

et al. 2017

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Cilia and eukaryotic flagella are threadlike cell extensions with motile and sensory functions. Their assembly requires intraflagellar transport (IFT), a bidirectional motor-driven transport of protein carriers along the axonemal microtubules. IFT moves ample amounts of structural proteins including tubulin into growing cilia likely explaining its critical role for assembly. IFT continues in non-growing cilia contributing to a variety of processes ranging from axonemal maintenance and the export of non-ciliary proteins to cell locomotion and ciliary signaling. Here, we discuss recent data on cues regulating the type, amount, and timing of cargo transported by IFT. A regulation of IFT-cargo interactions is critical to establish, maintain, and adjust ciliary length, protein composition, and function.

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“…2017). Chlamydomonas ciliary EVs carry ECM proteins and ECM-degrading proteases, including a proteolytic enzyme that degrades ECM necessary for hatching (L ong et al . 2016; W ood et al .…”

Section: Discussionmentioning

confidence: 99%

Extracellular matrix regulates morphogenesis and function of ciliated sensory organs inCaenorhabditis elegans

Vore

Knobel

Nguyen

et al. 2018

Preprint

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20 2 ECM regulates morphogenesis and function of ciliated sensory organs in 21 Caenorhabditis elegans 22 ABSTRACT 23 Cilia and extracellular vesicles (EVs) are signaling organelles that play important 24 roles in human health and disease. In C. elegans and mammals, the Autosomal 25 Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 and 26polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and 27 function in a sensory capacity, suggesting ancient conservation. Hence, the nematode 28 offers an excellent system in which to address central questions regarding the biology of 29 cilia, EVs, and the polycystins. We discovered an unexpected role of the mec-1, mec-5, 30 and mec-9 genes encoding extracellular matrix (ECM) components. We determined that 31 these ECM encoding genes regulate polycystin localization and function, ciliary EV 32 release, cilia length, dendritic morphology, and neuron-glia interactions. Abnormal ECM 33 and fibrosis are observed in ciliopathies such as ADPKD, nephronophthisis, and Biedl Syndrome. Our studies reveal multifaceted roles for ECM proteins in the ciliated 35 nervous system of the worm and provide a powerful new in vivo model to study the 36 relationship between ECM, the polycystins, and ciliopathies. 37 38 39 40 41 42 Cilia are antenna-like structures that project from many eukaryotic cells (WOOD 43 AND ROSENBAUM 2015). Cilia play essential roles in human development and health, with 44 ciliary defects resulting in syndromic ciliopathies (REITER AND LEROUX 2017). Cilia are 45 endowed with receptors, channels, and signaling components, enabling cilia to act as 46 cellular sensors. In addition to their sensory abilities, cilia may transmit signals via 47 submicroscopic extracellular vesicles (WANG AND BARR 2018; WOOD AND ROSENBAUM 48 2015). The mechanisms that enable a cilium to simultaneously send and receive 49 information remain mysterious.50Cilia and the extracellular matrix (ECM) share an intimate association, with cilia 51 projecting into and being surrounded by ECM (SEEGER-NUKPEZAH AND GOLEMIS 2012). 52ECM is made up of a network of interacting proteins that surround and support cells for 53 adhesive, structural and signaling functions (HYNES 2009). ECM is necessary for tissue 54 morphogenesis and homeostasis throughout the lifespan of an organism and 55 dynamically interacts with and regulates body systems, organs, and tissues. In the 56 brain and nervous system, ECM is important for neuronal development, anatomy, and 57 synaptic transmission. Dysregulation of ECM contributes to pathological conditions 58 such as invasive cancer and fibrosis (BONNANS et al. 2014). Fibrosis and abnormal ECM 59 are observed in ciliopathies such as autosomal dominant polycystic kidney disease 60 (ADPKD), nephronophthisis, and Bardet-Biedl Syndrome (SONG et al. 2017). 61 ADPKD is a genetic disorder characterized by the presence of fluid filled cysts 62 which form on and in the kidney epithelia lining renal tubules that replace normally 63 funct...

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Comparative Analysis of Ciliary Membranes and Ectosomes

Cited by 90 publications

References 34 publications

Glutamylation Regulates Transport, Specializes Function, and Sculpts the Structure of Cilia

Glutamylation Regulates Transport, Specializes Function, and Sculpts the Structure of Cilia

Protein transport in growing and steady‐state cilia

Extracellular matrix regulates morphogenesis and function of ciliated sensory organs inCaenorhabditis elegans

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