CCDC15 localizes to the centriole inner scaffold and controls centriole length and integrity

Arslanhan, Melis D.; Cengiz-Emek, Seyma; Odabasi, Ezgi; Steib, Emmanuelle; Hamel, Virginie; Guichard, Paul; Firat-Karalar, Elif Nur

doi:10.1083/jcb.202305009

Cited by 13 publications

(6 citation statements)

References 112 publications

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“…Importantly, U-ExM analysis revealed that HYLS1 mutation or HYLS1 loss leads to centrioles that are short or broken at their distal end, consistent with a weakened microtubule wall. Similar structural integrity phenotypes have been described upon loss of the centriole microtubule wall protein WDR90 and the centriole inner scaffold proteins HAUS6 and CCDC15 (Steib et al ., 2020; Schweizer et al ., 2021; Arslanhan et al ., 2023). Like HYLS1, WDR90 depletion has also been shown to impair the recruitment of the inner scaffold proteins POC5 and Centrin2 (Steib et al ., 2020).…”

Section: Discussionmentioning

confidence: 99%

Centriole structural integrity defects are a crucial feature of Hydrolethalus Syndrome

Curinha,

Huang,

Anglen

et al. 2024

Preprint

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Hydrolethalus Syndrome (HLS) is a lethal, autosomal recessive ciliopathy caused by the mutation of the conserved centriole protein HYLS1. However, how HYLS1 facilitates the centriole-based templating of cilia is poorly understood. Here, we show that mice harboring the HYLS1 disease mutation die shortly after birth and exhibit developmental defects that recapitulate several manifestations of the human disease. These phenotypes arise from tissue-specific defects in cilia assembly and function caused by a loss of centriole integrity. We show that HYLS1 is recruited to the centriole by CEP120 and functions to recruit centriole inner scaffold proteins that stabilize the centriolar microtubule wall. The HLS mutation disrupts the interaction of HYLS1 with CEP120 leading to HYLS1 displacement and degeneration of the centriole distal end. We propose that tissue-specific defects in centriole integrity caused by the HYLS1 mutation prevent ciliogenesis and drive HLS phenotypes.

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Section: Discussionmentioning

confidence: 99%

Centriole structural integrity defects are a crucial feature of Hydrolethalus Syndrome

Curinha,

Huang,

Anglen

et al. 2024

Preprint

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“…CCDC15 is located within the scaffold of the centriole and controls the length and integrity of the centriole. 30 KTN1, as an LncRNA, promotes tumor growth in hepatocellular carcinoma and exacerbates tumor progression in ovarian cancer. 31,32 MRPL14 not only promotes the biogenesis and mitochondrial translation of mitochondrial macroribosomal subunits, but also has certain relevance in diabetes retinopathy.…”

Section: Discussionmentioning

confidence: 99%

“…The results showed that the p ‐value in the HEIDI test of CCDC15 , KTN1 , MRPL14 , RPF2 , and CD151 was less than 0.05, indicating that the correlation of these genes may be caused by pleiotropy. CCDC15 is located within the scaffold of the centriole and controls the length and integrity of the centriole 30 . KTN1 , as an LncRNA, promotes tumor growth in hepatocellular carcinoma and exacerbates tumor progression in ovarian cancer 31,32 .…”

Section: Discussionmentioning

confidence: 99%

Resting CD4 regulatory T cell and neuroblastoma: A Mendelian randomization study

Wang,

Wang

2024

Pediatric Discovery

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Neuroblastoma (NB) is a common extracranial solid tumor in children, and currently our understanding of the molecular mechanisms underlying tumor progression is not very thorough. In clinical practice, although the prognosis and survival rates of NB patients in the low‐risk and medium‐risk groups are still acceptable, the prognosis and survival rates of NB patients in the high‐risk group are extremely poor. Therefore, improving awareness of NB tumors is crucial for improving the treatment status of NB patients in clinical practice. So we collected common tumor exposure factors and performed multiple Mendelian randomization (MR) analysis on NB, and ultimately determined that the increase in Resting CD4 regulatory T cell was positively correlated with the occurrence and development of NB. In addition, we also used the network pharmacology algorithm proximity to screen the NB chemotherapy drug papain and reasonably speculated that there is an interaction between papain and CD4 regulatory T cell in the chemotherapy of NB patients.

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“…Within the central core, a helical inner scaffold is formed in G2-phase of the first cell cycle after centriole birth, imparts structural integrity upon the centriole (Le Steib et al, 2020), and recruits proteins, including gamma-tubulin, to the lumen of the centriole (Schweizer et al, 2021). This scaffold is formed of POC5, POC1B, FAM161A, WDR90, and CCDC15 and contacts all three (A-, B-, and C-) tubules (Arslanhan et al, 2023;Steib et al, 2020). WDR90 has been proposed to form the inner junction stem bridging the inner scaffold and the interface between the A-and B-tubules (Steib et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture

Pudlowski,

Xu,

Milenkovic

et al. 2024

Preprint

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Centrioles have a unique, conserved architecture formed by three linked triplet microtubules arranged in nine-fold symmetry. The mechanisms by which these triplet microtubules are formed are not understood, but likely involve the noncanonical tubulins delta-tubulin and epsilon-tubulin. Previously, we found that human cells deficient in delta-tubulin or epsilon-tubulin form abnormal centrioles, characterized by an absence of triplet microtubules, lack of central core protein POC5, and a futile cycle of centriole formation and disintegration (Wang et al., 2017). Here, we show that human cells lacking either of the associated proteins TEDC1 and TEDC2 have these same phenotypes. Using ultrastructure expansion microscopy, we identified the roles of these proteins and triplet microtubules in centriole architecture by mapping the locations of centriolar proteins throughout the cell cycle. We find that mutant centrioles have normal architecture during S-phase. By G2-phase, mutant centrioles grow to the same length as control centrioles, but fail to recruit inner scaffold proteins of the central core. Instead, the inner lumen of centrioles is filled with an expanded proximal region, indicating that these proteins, or the triplet microtubules themselves, may be required for recruiting central core proteins and restricting the length of the proximal end. During mitosis, the mutant centrioles elongate further before fragmenting and disintegrating. All four proteins physically interact and TEDC1 and TEDC2 are capable of interacting in the absence of the tubulins. These results support an AlphaFold Multimer structural prediction model for the tetrameric complex, in which delta-tubulin and epsilon-tubulin are predicted to form a heterodimer. TEDC1 and TEDC2 localize to centrosomes and are mutually dependent on each other and on delta-tubulin and epsilon-tubulin for localization. These results indicate that delta-tubulin, epsilon-tubulin, TEDC1, and TEDC2 function together in promoting robust centriole architecture. This work also lays the groundwork for future dissection of this complex, which will provide a basis for determining the mechanisms that underlie the assembly and interplay between compound microtubules and inner centriole structure.

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CCDC15 localizes to the centriole inner scaffold and controls centriole length and integrity

Cited by 13 publications

References 112 publications

Centriole structural integrity defects are a crucial feature of Hydrolethalus Syndrome

Centriole structural integrity defects are a crucial feature of Hydrolethalus Syndrome

Resting CD4 regulatory T cell and neuroblastoma: A Mendelian randomization study

A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture

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