Spatial and proteomic profiling reveals centrosome‐independent features of centriolar satellites

Gheiratmand, Ladan; Coyaud, Étienne; Gupta, Gagan D.; Laurent, Estelle; Hasegan, Monica; Prosser, Suzanna L.; Gonçalves, João; Raught, Brian; Pelletier, Laurence

doi:10.15252/embj.2018101109

Cited by 90 publications

(155 citation statements)

References 101 publications

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“…CCDC57 was one of the uncharacterized proteins that stood out in these maps due to its high proximity to centriole duplication proteins. Notably, CCDC57 was recently identified as a component of the centriolar satellite interactome, which corroborates the functional relationship between centriolar satellites and centriole duplication (Gheiratmand et al, 2019). Here, we characterized CCDC57 as a centriole duplication protein required for recruitment of the microcephaly-associated proteins CEP63, CEP152, and PLK4 to the centrosome.…”

Section: Introductionsupporting

confidence: 83%

CCDC57 Cooperates with Microtubules and Microcephaly Protein CEP63 and Regulates Centriole Duplication and Mitotic Progression

et al. 2020

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Section: Introductionsupporting

confidence: 83%

CCDC57 Cooperates with Microtubules and Microcephaly Protein CEP63 and Regulates Centriole Duplication and Mitotic Progression

et al. 2020

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“…Notably, fibrogranular material in MCCs was shown to contain the protein PCM1 39 , which is also required to scaffold the assembly of the 'pericentriolar satellites' that are found in non-MCCs. It is therefore possible that the fibrogranular material is functionally equivalent to the pericentriolar satellites of non-MCCs [40][41][42][43] . Additional studies will be required to identify the minimal components involved in centriole assembly and number control, and to define the role of DEUP1 and the deuterosome in MCCs.…”

Section: Discussionmentioning

confidence: 99%

Massive centriole production can occur in the absence of deuterosomes in multiciliated cells

et al. 2019

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ulticiliated cells (MCCs) contain tens of motile cilia that beat to drive fluid flow across epithelial surfaces. Multiciliated cells are present in the respiratory tract, brain ventricles and reproductive systems. Defects in motile-cilia formation or beating lead to the development of hydrocephaly, lethal respiratory symptoms and fertility defects 1-4. A centriole, or basal body, serves as a template for the cilium axoneme. Centriole duplication is tightly controlled in cycling cells so that a single new procentriole forms adjacent to each of the two parent centrioles 5. However, MCC progenitors with two parent centrioles produce tens to hundreds of additional new centrioles to nucleate multiple motile cilia 1. Steric constraints imposed by the 'centriolar' pathway seem to restrict the number of procentrioles that can be nucleated by the parent centrioles. Centriole amplification is therefore thought to rely on the assembly of dozens of MCCspecific organelles called deuterosomes, which each nucleate tens of procentrioles 6-14. Deuterosomes are assembled during centriole amplification and support the growth of approximately 90% of the procentrioles formed in mammalian MCCs 12,14. Deuterosomes have been proposed to be nucleated from the younger parent centriole 12 but can form spontaneously in a cloud of pericentriolar material (PCM) in MCCs depleted of the parent centrioles 15-17. Many of the proteins required for centriole formation in MCCs are common to centriole duplication 11-15,18-23. However, DEUP1 (CCDC67, alternate gene name) has been identified as a deuterosome-specific protein that arose from a gene-duplication event of the centriolar gene Cep63. Recent data suggest that Deup1 evolved to enable the formation of deuterosomes and the generation of large numbers of centrioles 14. In this manuscript, we interrogate the function of the deuterosome in MCCs from mouse and from Xenopus laevis. Surprisingly, our findings reveal that deuterosomes are dispensable for centriole amplification and multiciliogenesis both in vitro and in vivo. Moreover, we show that neither deuterosomes nor parent centrioles are required for MCCs to amplify the correct number of centrioles. These findings raise new questions about the evolutionary role of deuterosome during multiciliogenesis and the mechanisms regulating centriole number in MCCs. Results Generation of a Deup1-knockout mouse. To examine the role of the deuterosome in multiciliogenesis we created a Deup1-knockout mouse by replacing a region from within exon 2 to within exon 7 of the Deup1 gene with a LacZ reporter (Extended Data Fig. 1a). Reverse Transcription-quantitative PCR on brain and testes samples showed that the messenger RNA levels of Deup1 were reduced by at least tenfold in Deup1-knockout compared with control mice (Extended Data Fig. 1b,c). To examine the process of multiciliogenesis in Deup1 −/− cells, we utilized in vitro cultures of mouse tracheal epithelial cells (mTECs) or ependymal cells 24,25. Consistent with the absence of Deup1 mRNA, DEUP1 foci were a...

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“…EMBL EBI Expression Atlas ebi.ac.uk/gxa). Moreover, two independent proximity labeling studies identified LUZP1 as a proximal interactor of centriole (35) and centriolar satellite-related proteins (45). Here, we report that LUZP1 forms a basket-like 3D structure surrounding the proximal end of both centrioles.…”

Section: Discussionmentioning

confidence: 99%

LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is altered in Townes-Brocks Syndrome

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Bermejo-Arteagabeitia

et al. 2019

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36Primary cilia are sensory organelles that are crucial for cell signaling during 37 development and organ homeostasis. Cilia arise from the centrosome and their 38 formation is governed by numerous regulatory factors. We show that the leucine-zipper 39 protein LUZP1 localizes to the pericentriolar material and actin cytoskeleton. Using 40TurboID proximity labeling and pulldowns, LUZP1 associates with factors linked to 41 centrosome and actin filaments. Loss of LUZP1 reduces F-actin levels, facilitating 42 ciliogenesis and altering Sonic Hedgehog signaling, pointing to a key role in the 43 cytoskeleton-cilia interdependency. Moreover, we show that LUZP1 interacts with a 44 truncated form of the transcription factor SALL1 that causes Townes-Brocks Syndrome. 45 TBS is characterized by digit, heart and kidney malformations and is linked in part to 46 defective cilia. Truncated SALL1 increases the ubiquitin proteasome-mediated 47 51Primary cilia are sensory organelles that have a crucial role in cell signaling, 52 polarity and protein trafficking during development and organ homeostasis. 53 Importantly, the involvement of primary cilia in the above-mentioned processes is 54 frequently due to its role in Sonic Hedgehog (Shh) pathway regulation (1). Briefly, Shh 55 activation through its receptor PTCH1 leads to ciliary enrichment of the transmembrane 56 protein Smoothened (SMO), with concomitant conversion of the transcription factor 57 GLI3 from a cleaved repressor form to a full-length activator form, leading to activation 58 of Shh target genes. Two such genes are PTCH1 and GLI1 (encoding the Shh receptor 59 and a transcriptional activator, respectively), exemplifying the feedback and fine-tuning 60 of the Shh pathway. 61Cilia arise from the centrosome, a cellular organelle composed of two barrel-62 shaped microtubule-based structures called the centrioles. Primary cilia formation is 63 very dynamic throughout the cell cycle. Cilia are nucleated from the mother centriole 64 (MC) at the membrane-anchored basal body upon entry into the G0 phase, and they 65 reabsorb as cells progress from G1 to S phase, completely disassembling in mitosis (2). 66Centrioles are surrounded by protein-based matrix pericentriolar material (PCM) (3, 4). 67In eukaryotic cells, PCM proteins are concentrically arranged around a centriole in a 68 highly organized manner (5-8). Based on this observation, proper positioning and 69 organization of PCM proteins may be important for promoting different cellular 70 processes in a spatially regulated way (9). Not surprisingly, aberrations in the function 71 of PCM scaffolds are also associated with many human diseases, including cancer and 72 ciliopathies (10, 11). 73Cilia assembly and disassembly are regulated by diverse factors, including the 74 main cilia suppressor proteins CCP110 and CEP97 and the actin cytoskeleton. CCP110 75 4 and CEP97 form a complex that, when removed from the MC, allows ciliogenesis (12). 76The regulation of actin dynamics is also considered a major ciliogenesis driver in 7...

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Spatial and proteomic profiling reveals centrosome‐independent features of centriolar satellites

Cited by 90 publications

References 101 publications

CCDC57 Cooperates with Microtubules and Microcephaly Protein CEP63 and Regulates Centriole Duplication and Mitotic Progression

CCDC57 Cooperates with Microtubules and Microcephaly Protein CEP63 and Regulates Centriole Duplication and Mitotic Progression

Massive centriole production can occur in the absence of deuterosomes in multiciliated cells

LUZP1, a novel regulator of primary cilia and the actin cytoskeleton, is altered in Townes-Brocks Syndrome

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