The daughter centriole controls ciliogenesis by regulating Neurl-4 localization at the centrosome

Loukil, Abdelhalim; Tormanen, Kati; Sütterlin, Christine

doi:10.1083/jcb.201608119

Cited by 39 publications

(46 citation statements)

References 63 publications

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“…Anti‐PCM1 antibody was generated and used for immunofluorescence as previously described . Other primary antibodies used for immunofluorescence in this study were rabbit anti‐PCM1 (Proteintech—19856‐1‐AP) at 1:1,000, goat anti‐PCM1 (E‐5, Santa Cruz Biotechnology—sc50164) at 1:1,000, mouse anti‐γ‐tubulin (GTU‐88; Sigma‐Aldrich—T6557) at 1:4,000, mouse anti‐GFP (3e6; Invitrogen—11120) at 1:750, mouse anti‐acetylated tubulin (6‐11‐B; Sigma‐Aldrich—T6793)) at 1:10,000, mouse anti‐polyglutamylated tubulin (GT335, Adipogen—AG‐20B‐0020) at 1:500, mouse anti‐Smo (Santa Cruz Biotechnology—sc166685) at 1:500, mouse anti‐Arl13b (Neuromab—75‐287) at 1:1,000, rabbit anti‐IFT88 (Proteintech—13967‐1‐AP) at 1:200 , mouse anti‐MIB1 (Santa Cruz Biotechnology—sc‐393811) at 1:500, rabbit anti‐CP110 (Proteintech—12780‐1‐AP) at 1:200 , rabbit anti‐Talpid3 (Proteintech—24421‐1‐AP) at 1:500 , rabbit anti‐Cep290 (Abcam—ab84870) at 1:750 , rat anti‐ZO1 (Santa Cruz Biotechnology—sc33725) at 1:200, rabbit anti‐beta‐catenin (Proteintech—51062‐2‐AP) at 1:500, and mouse anti‐Cep164 at 1:500 . Secondary antibodies used for immunofluorescence experiments were Alexa Fluor 488‐, 568‐, or 633‐coupled (Life Technologies), and they were used at 1:2,000.…”

Section: Methodsmentioning

confidence: 99%

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

et al. 2019

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Centriolar satellites are ubiquitous in vertebrate cells. They have recently emerged as key regulators of centrosome/cilium biogenesis, and their mutations are linked to ciliopathies. However, their precise functions and mechanisms of action remain poorly understood. Here, we generated a kidney epithelial cell line ( IMCD 3) lacking satellites by CRISPR /Cas9‐mediated PCM 1 deletion and investigated the cellular and molecular consequences of satellite loss. Cells lacking satellites still formed full‐length cilia but at significantly lower numbers, with changes in the centrosomal and cellular levels of key ciliogenesis factors. Using these cells, we identified new ciliary functions of satellites such as regulation of ciliary content, Hedgehog signaling, and epithelial cell organization in three‐dimensional cultures. However, other functions of satellites, namely proliferation, cell cycle progression, and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites affects transcription scarcely, but significantly alters the proteome. Importantly, the centrosome proteome mostly remains unaltered in the cells lacking satellites. Together, our findings identify centriolar satellites as regulators of efficient cilium assembly and function and provide insight into disease mechanisms of ciliopathies.

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Section: Methodsmentioning

confidence: 99%

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

et al. 2019

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“…[55][56][57] CP110 associates with centrosomal protein (CEP97), centrosomal protein 290 (CEP290), and Talpid3 and acts as a cap at the distal end of centrioles to block the conversion from the mother centriole to the basal body. [61,62] NEURL4 localizes to the daughter centriole in cycling RPE1 cells. [56,60] The removal of CP110 is also regulated by neuralized E3 ubiquitin protein ligase 4 (NEURL4).…”

Section: Assembly Of Primary Cilia Responding To Serum Withdrawalmentioning

confidence: 99%

“…[62,63] Fourth, the ciliary vesicle fuses with the plasma membrane. [62,63] Fourth, the ciliary vesicle fuses with the plasma membrane.…”

Section: Assembly Of Primary Cilia Responding To Serum Withdrawalmentioning

confidence: 99%

Primary Cilia as Signaling Hubs in Health and Disease

et al. 2018

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Primary cilia detect extracellular cues and transduce these signals into cells to regulate proliferation, migration, and differentiation. Here, the function of primary cilia as signaling hubs of growth factors and morphogens is in focus. First, the molecular mechanisms regulating the assembly and disassembly of primary cilia are described. Then, the role of primary cilia in mediating growth factor and morphogen signaling to maintain human health and the potential mechanisms by which defects in these pathways contribute to human diseases, such as ciliopathy, obesity, and cancer are described. Furthermore, a novel signaling pathway by which certain growth factors stimulate cell proliferation through suppression of ciliogenesis is also described, suggesting novel therapeutic targets in cancer.

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“…Recently, the daughter centriole has been implied in ciliogenesis due to its proximity to the mother centriole (Loukil et al, 2017). We therefore asked whether lack of cilia upon LRRC45 depletion in WT and CEP250 KO RPE1 cells correlated with the distance between both centrioles ( Figure 2).…”

Section: Lrrc45 Contributes To Cilia Formation Independently Of C-nap1mentioning

confidence: 98%

Analysis of LRRC45 indicates cooperative functions of distal appendages at early steps of ciliogenesis

Kurtulmus

Yuan

Schuy

et al. 2017

Preprint

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Cilia perform essential signalling functions during development and tissue homeostasis. Ciliary malfunction causes a variety of diseases, named ciliopathies. The key role that the mother centriole plays in cilia formation can be attributed to appendage proteins that associate exclusively with the mother centriole. The distal appendages form a platform that docks early ciliary vesicles and removes CP110/Cep97 inhibitory complexes from the mother centriole. Here, we analysed the role played by LRRC45 in appendage formation and ciliogenesis. We show that the core appendage proteins Cep83 and SCLT1 recruit LRRC45 to the mother centriole.Once there LRRC45 recruits FBF1. The association of LRRC45 with the basal body of primary and motile cilia in differentiated and stem cells reveals a broad function in ciliogenesis. In contrast to the appendage components Cep164 and Cep123, LRRC45 was neither essential for docking of early ciliary vesicles nor for removal of CP110.Rather, LRRC45 promotes cilia biogenesis in CP110-uncapped centrioles by organising centriolar satellites and promoting the docking of Rab8 GTPase-positive vesicles. We propose that, instead of acting solely as a platform to recruit early vesicles, centriole appendages form discrete scaffolds of cooperating proteins that execute specific functions that promote the initial steps of ciliogenesis.not peer-reviewed)

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The daughter centriole controls ciliogenesis by regulating Neurl-4 localization at the centrosome

Cited by 39 publications

References 63 publications

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

Primary Cilia as Signaling Hubs in Health and Disease

Analysis of LRRC45 indicates cooperative functions of distal appendages at early steps of ciliogenesis

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