Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release

Salinas, Raquel Y.; Pearring, Jillian N.; Ding, Jindong; Spencer, William J.; Hao, Ying; Arshavsky, Vadim Y.

doi:10.1083/jcb.201608081

Cited by 125 publications

(139 citation statements)

References 52 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%

“…C. elegans amphid channel cilia, mammalian olfactory cilia, and mammalian renal primary cilia possess a proximal doublet region followed by a distal A-tubule singlet region [1, 2, 4, 5]. Another ciliary specialization is the ability to produce extracellular vesicles (EVs) called ectosomes [6–11]. The molecular underpinnings and functions of these specializations are only beginning to be appreciated.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…Cilia (also known as flagella) are important organelles needed for cell motility, morphogenesis, sensory perception, and several signaling pathways, such as sonic hedgehog and PDGFRa signaling (Huangfu et al, 2003;Kohl et al, 2003;San Agustin et al, 2015;Salinas et al, 2017;Schneider et al, 2005). Cilia are tail-like appendages protruding from the cell surface of nearly every eukaryotic cell type and are found on various unicellular organisms and on almost all cells in the mammalian body.…”

Section: Introductionmentioning

confidence: 99%

Binding of IFT22 to the intraflagellar transport complex is essential for flagellum assembly

et al. 2019

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Intraflagellar transport (IFT) relies on motor proteins and the IFT complex to construct cilia and flagella. The IFT complex subunit IFT22/RabL5 has sequence similarity with small GTPases although the nucleotide specificity is unclear because of non‐conserved G4/G5 motifs. We show that IFT22 specifically associates with G‐nucleotides and present crystal structures of IFT22 in complex with GDP, GTP, and with IFT74/81. Our structural analysis unravels an unusual GTP/GDP‐binding mode of IFT22 bypassing the classical G4 motif. The GTPase switch regions of IFT22 become ordered upon complex formation with IFT74/81 and mediate most of the IFT22‐74/81 interactions. Structure‐based mutagenesis reveals that association of IFT22 with the IFT complex is essential for flagellum construction in Trypanosoma brucei although IFT22 GTP‐loading is not strictly required.

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“…These cilium-derived ECVs are taken up by the neighboring retinal pigmented epithelium where the retinol is reduced and transported back to the photoreceptor to regenerate function Opsins [166]. At the base of the outer segment, membrane discs are formed by membrane evagination and are retained within the outer segment and restrained from being shed by the disc-specific protein Peripherin [167,168]. The simultaneous processes of controlled vesicular shedding at the tip and membrane disc formation at the base allows continuous renewal of the outer segments.…”

Section: Ciliary-derived Vesicles Participate In Diverse Cellular Funmentioning

confidence: 99%

How the Ciliary Membrane Is Organized Inside-Out to Communicate Outside-In

2018

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Cilia, organelles that move to execute functions like fertilization and signal to execute functions like photoreception and embryonic patterning, are composed of a core of nine-fold doublet microtubules overlain by a membrane. Distinct types of cilia display distinct membrane morphologies, ranging from simple domed cylinders to the highly ornate invaginations and membrane disks of photoreceptor outer segments. Critical for the ability of cilia to signal, both the protein and the lipid compositions of ciliary membranes are different from those of other cellular membranes. This specialization presents a unique challenge for the cell as, unlike membrane-bounded organelles, the ciliary membrane is contiguous with the surrounding plasma membrane. This distinct ciliary membrane is generated in concert with multiple membrane remodeling events that comprise the process of ciliogenesis. Once the cilium is formed, control of ciliary membrane composition relies on discrete molecular machines, including a barrier to membrane proteins entering the cilium at a specialized region of the base of the cilium called the transition zone and a trafficking adaptor that controls G protein-coupled receptor (GPCR) localization to the cilium called the BBSome. The ciliary membrane can be further remodeled by the removal of membrane proteins by the release of ciliary extracellular vesicles that may function in intercellular communication, removal of unneeded proteins or ciliary disassembly. Here, we review the structures and transport mechanisms that control ciliary membrane composition, and discuss how membrane specialization enables the cilium to function as the antenna of the cell.

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Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release

Cited by 125 publications

References 52 publications

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

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

Binding of IFT22 to the intraflagellar transport complex is essential for flagellum assembly

How the Ciliary Membrane Is Organized Inside-Out to Communicate Outside-In

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