bims-bicyki Biomed News
on Bicaudal-C1 and interactors in cystic kidney disease
Issue of 2022–09–18
fourteen papers selected by
Céline Gagnieux, École Polytechnique Fédérale de Lausanne
  1. Clinical Utility and Tolerability of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD).
  2. Endothelium-Specific Deficiency of Polycystin-1 Promotes Hypertension and Cardiovascular Disorders.
  3. Shared pathobiology identifies AMPK as a therapeutic target for obesity and autosomal dominant polycystic kidney disease.
  4. A Systematic Review of Reported Outcomes in ADPKD Studies.
  5. Native nephrectomy and arterial embolization of native kidney in autosomal dominant polycystic kidney disease patients: indications, timing and postoperative outcomes. A systematic review.
  6. Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment.
  7. [Bilateral laparoscopic nephrectomy for polycystic kidney disease].
  8. Forensic Autopsy Reveals Novel Pathogenic Variant of PKD1 Associated With Polycystic Kidney Disease.
  9. Cardiovascular Outcomes in Kidney Transplant Recipients With ADPKD.
  10. A Novel Homozygous Variant in GAS2L2 in Two Sisters with Primary Ciliary Dyskinesia.
  11. The distal central pair segment is structurally specialised and contributes to IFT turnaround and assembly of the tip capping structures in Chlamydomonas flagella.
  12. Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphology.
  13. Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif.
  14. Bld10p/Cep135 determines the number of triplets in the centriole independently of the cartwheel.
  1. Drug Healthc Patient Saf. 2022 ;14 147-159
    Clinical Utility and Tolerability of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD).
    Rupesh Raina, Ahmad Houry, Pratik Rath, Guneive Mangat, Davinder Pandher, Muhammad Islam, Ala'a Grace Khattab, Joseph K Kalout, Sumedha Bagga.
      Autosomal dominant polycystic kidney disease, also known as ADPKD, is the most common hereditary kidney disease, affecting different age groups. ADPKD can eventually lead to end-stage renal disease. The etiology of ADPKD is genetic, resulting in the formation of cysts containing fluids on the kidneys. Patients with ADPKD present a range of symptoms following a decline in kidney function. Pain, stones, proteinuria and osteoporosis are few of the many symptoms, resulting from decreased kidney function. Tolvaptan, a selective V2 receptor antagonist, is the etiological treatment used for ADPKD. In this paper, we conducted a systematic review of the literature between 2011 and 2021 to gather data regarding the tolerability and efficacy of tolvaptan use in ADPKD. A total of 22 trials were reviewed. Tolvaptan efficacy in the trials was measured using changes in eGFR or changes in total kidney volume. Results showed that tolvaptan use in ADPKD was associated with a slower decline in kidney function and a decrease in total kidney volume. Side effects of this drug include polyuria, nocturia and polydipsia along with hepatotoxicity. The two biggest trials, TEMPO and REPRISE, change in eGFR from pre-treatment baseline to post-treatment was 1.3 mL/min/1.73 for REPRISE and 1 mL/min/1.73 for TEMPO 3:4. A mean decrease of 49% in total kidney volume from baseline to post-treatment was found in the TEMPO 3:4 study.
    Keywords:  ADPKD; tolvaptan
    DOI:  https://doi.org/10.2147/DHPS.S338050
  2. Hypertension. 2022 Sep 12. 101161HYPERTENSIONAHA12219057
    Endothelium-Specific Deficiency of Polycystin-1 Promotes Hypertension and Cardiovascular Disorders.
    Mouad Hamzaoui, Deborah Groussard, Dorian Nezam, Zoubir Djerada, Gaspard Lamy, Virginie Tardif, Anais Dumesnil, Sylvanie Renet, Valery Brunel, Dorien J M Peters, Laurence Chevalier, Mélanie Hanoy, Paul Mulder, Vincent Richard, Jeremy Bellien, Dominique Guerrot.
       BACKGROUND: Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disease and is generally due to mutations in PKD1 and PKD2, encoding polycystins 1 and 2. In autosomal dominant polycystic kidney disease, hypertension and cardiovascular disorders are highly prevalent, but their mechanisms are partially understood.
    METHODS: Since endothelial cells express the polycystin complex, where it plays a central role in the mechanotransduction of blood flow, we generated a murine model with inducible deletion of Pkd1 in endothelial cells (Cdh5-CreERT2;Pkd1fl/fl) to specifically determine the role of endothelial polycystin-1 in autosomal dominant polycystic kidney disease.
    RESULTS: Endothelial deletion of Pkd1-induced endothelial dysfunction, as demonstrated by impaired flow-mediated dilatation of resistance arteries and impaired relaxation to acetylcholine, increased blood pressure and prevented the normal development of arteriovenous fistula. In experimental chronic kidney disease induced by subtotal nephrectomy, endothelial deletion of Pkd1 further aggravated endothelial dysfunction, vascular remodeling, and heart hypertrophy.
    CONCLUSIONS: Altogether, this study provides the first in vivo demonstration that specific deletion of Pkd1 in endothelial cells promotes endothelial dysfunction and hypertension, impairs arteriovenous fistula development, and potentiates the cardiovascular alterations associated with chronic kidney disease.
    Keywords:  autosomal dominant polycystic kidney disease; chronic kidney disease; ciliopathy; endothelial dysfunction; hypertension; polycystin
    DOI:  https://doi.org/10.1161/HYPERTENSIONAHA.122.19057
  3. Front Mol Biosci. 2022 ;9 962933
    Shared pathobiology identifies AMPK as a therapeutic target for obesity and autosomal dominant polycystic kidney disease.
    Ioan-Andrei Iliuta, Xuewen Song, Lauren Pickel, Amirreza Haghighi, Ravi Retnakaran, James Scholey, Hoon-Ki Sung, Gregory R Steinberg, York Pei.
      Autosomal dominant polycystic kidney disease (ADPKD) is the most common Mendelian kidney disease, affecting approximately one in 1,000 births and accounting for 5% of end-stage kidney disease in developed countries. The pathophysiology of ADPKD is strongly linked to metabolic dysregulation, which may be secondary to defective polycystin function. Overweight and obesity are highly prevalent in patients with ADPKD and constitute an independent risk factor for progression. Recent studies have highlighted reduced AMP-activated protein kinase (AMPK) activity, increased mammalian target of rapamycin (mTOR) signaling, and mitochondrial dysfunction as shared pathobiology between ADPKD and overweight/obesity. Notably, mTOR and AMPK are two diametrically opposed sensors of energy metabolism that regulate cell growth and proliferation. However, treatment with the current generation of mTOR inhibitors is poorly tolerated due to their toxicity, making clinical translation difficult. By contrast, multiple preclinical and clinical studies have shown that pharmacological activation of AMPK provides a promising approach to treat ADPKD. In this narrative review, we summarize the pleiotropic functions of AMPK as a regulator of cellular proliferation, macromolecule metabolism, and mitochondrial biogenesis, and discuss the potential for pharmacological activation of AMPK to treat ADPKD and obesity-related kidney disease.
    Keywords:  AMPK; autosomal dominant polycystic kidney disease; energy metabolism; metabolic dysregulation; obesity
    DOI:  https://doi.org/10.3389/fmolb.2022.962933
  4. Kidney Int Rep. 2022 Sep;7(9): 1964-1979
    A Systematic Review of Reported Outcomes in ADPKD Studies.
    Sara S Jdiaa, Nedaa M Husainat, Razan Mansour, Mohamad A Kalot, Kerri McGreal, Fouad T Chebib, Ronald D Perrone, Alan Yu, Reem A Mustafa.
       Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic kidney disease. Studies of ADPKD presented results using different outcome measures. We aimed to summarize outcomes reported in ADPKD studies, including composite outcomes.
    Methods: We conducted a systematic review of published studies that included patients with ADPKD and measured kidney-related outcomes. We searched published databases and included all studies regardless of design with at least 100 participants for observational studies. We excluded studies that were limited to dialysis, transplant, or pregnancy outcomes in patients with ADPKD.
    Results: This review includes data from 175 published articles (49 randomized controlled trials, 2 interventional clinical trials, 30 post hoc analyses, and 94 observational studies). We identified 214 different outcomes, and we categorized them into the 24 main outcome domains. In addition, the review identified 13 articles that reported 9 different composite outcomes.
    Conclusion: The finding highlights the inconsistency in the outcomes reported by researchers and how they are measured in ADPKD studies. The variability in the outcomes reported supports the need to standardize outcomes in ADPKD studies.
    Keywords:  ADPKD; PKD; polycystic kidney disease
    DOI:  https://doi.org/10.1016/j.ekir.2022.06.012
  5. Minerva Urol Nephrol. 2022 Sep 12.
    Native nephrectomy and arterial embolization of native kidney in autosomal dominant polycystic kidney disease patients: indications, timing and postoperative outcomes. A systematic review.
    EAU - Young Academic Urologist (YAU) group of Kidney Transplant
       INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common causes of a need of renal replacement therapy. The need (elective vs. systematic) and timing of native kidney nephrectomy (before, after or during kidney transplantation) is a matter of debate and alternatives to surgery, mainly transcatheter arterial embolization have been explored. We performed a systematic review to report all available evidence on postintervention outcomes of native nephrectomy and arterial embolization in ADPKD patients.
    EVIDENCE ACQUISITION: A search on Medline, Embase, and Cochrane databases was performed to identify all studies reporting outcomes of native nephrectomy or arterial embolization in APKDs.
    EVIDENCE SYNTHESIS: Concerning native nephrectomy, a total of 3,626 patients in 37 studies were included with 735, 210 and 2,681 patients who underwent native nephrectomy respectively before, after or during kidney transplantation. Major complications were 12.2% in unilateral nephrectomy before transplantation, 25.0% in bilateral nephrectomy before transplantation, 17.7% in unilateral nephrectomy during transplantation, 20.8% in bilateral nephrectomy during transplantation and 23.8% in unilateral and bilateral nephrectomy after transplantation. A total of 230 patients in 7 series of arterial embolization were included. All arterial embolization were performed before transplantation. Mean volume reduction ranged from 36.3% at 3 months to 49% at 6 months. The major post-intervention complication rate was 1%.
    CONCLUSIONS: Unilateral native nephrectomy before kidney transplantation was associated with the lowest major postoperative complication rate and appears to be the preferred strategy. Arterial embolization reduces kidney volume by 49% at 6 months. Arterial embolization could be considered when the reduction in size of the native kidney is not urgent.
    DOI:  https://doi.org/10.23736/S2724-6051.22.04972-2
  6. Nephron. 2022 Sep 09. 1-6
    Creatine Kinase Elevation in Autosomal Dominant Polycystic Kidney Disease Patients on Tolvaptan Treatment.
    Diana Rodríguez-Espinosa, José Jesús Broseta, Carla Bastida, María Isabel Álvarez-Mora, Carlos Nicolau, Cristina Alvarez, Irene Agraz-Pamplona, Maya Sánchez-Baya, Mónica Furlano, César Ruiz, Luis F Quintana, Gastón J Piñeiro, Esteban Poch, Roser Torra-Balcells, Miquel Blasco.
       BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of end-stage kidney disease. Currently, tolvaptan is the only treatment that has proven to delay disease progression. The most notable side effect of this therapy is drug-induced liver injury; however, recently, there have been two reports of creatine kinase (CK) elevation in ADPKD patients on tolvaptan treatment. We set out to monitor and determine the actual incidence of CK elevation and evaluate its potential association with other clinical factors.
    METHODS: This is an observational retrospective multicenter study performed in rapidly progressive ADPKD patients on tolvaptan treatment from Barcelona, Spain. Laboratory tests, demographics, treatment dose, and reported symptoms were collected from October 2018 to March 2021.
    RESULTS: Ninety-five patients initiated tolvaptan treatment during follow-up. The medication had to be discontinued in 31 (32.6%) patients, primarily due to aquaretic effects (12.6%), elevated liver enzymes (8.4%), and symptomatic or persistently elevated CK levels (3.2%). Moreover, a total of 27 (28.4%) patients had elevated CK levels, with most of them being either transient (12.6%), mild and asymptomatic (4.2%), or resolved after dose reduction (3.2%) or temporary discontinuation (2.1%).
    CONCLUSION: We pre-sent the largest cohort that has monitored CK levels in a real-life setting, finding them elevated in 28.4% of patients. More research and monitoring will help us understand the clinical implications and the pathophysiological mechanism of CK elevation in this population.
    Keywords:  ADPKD; Creatine-kinase; Side effect; Tolvaptan
    DOI:  https://doi.org/10.1159/000526368
  7. Urologiia. 2022 Sep; 71-74
    [Bilateral laparoscopic nephrectomy for polycystic kidney disease].
    T R Biktimirov, A G Martov, R G Biktimirov, A V Baranov, I A Miloserdov, A A Kaputovskiy, A M Khitrikh, N A Amosov.
      A clinical case of surgical treatment of a patient with autosomal dominant type of polycystic kidney disease, stage 5 of chronic kidney disease and secondary arterial hypertension is presented in the article. The technique of single-stage bilateral laparoscopic nephrectomy, patented by the authors, is described. The practicability and safety of a simultaneous bilateral procedures was demonstrated, as well as the advantage of laparoscopic access for this type of surgical interventions. The successful and prompt procedure allowed the patient to undergone to allotransplantation of a cadaveric kidney as soon as possible.
    Keywords:  ADPKD; bilateral nephrectomy; cysts; laparoscopic nephrectomy; polycystic kidney disease
  8. Am J Forensic Med Pathol. 2022 Sep 12.
    Forensic Autopsy Reveals Novel Pathogenic Variant of PKD1 Associated With Polycystic Kidney Disease.
    John C Walsh, Lynn M Messersmith, Jesse Fitzgerald, Mauricio J De Castro.
      
    DOI:  https://doi.org/10.1097/PAF.0000000000000795
  9. Kidney Int Rep. 2022 Sep;7(9): 1991-2005
    Cardiovascular Outcomes in Kidney Transplant Recipients With ADPKD.
    Maroun Chedid, Hasan-Daniel Kaidbay, Stijn Wigerinck, Yaman Mkhaimer, Byron Smith, Dalia Zubidat, Imranjot Sekhon, Reddy Prajwal, Parikshit Duriseti, Naim Issa, Ziad M Zoghby, Christian Hanna, Sarah R Senum, Peter C Harris, LaTonya J Hickson, Vicente E Torres, Vuyisile T Nkomo, Fouad T Chebib.
       Introduction: Cardiovascular disease leads to high morbidity and mortality in patients with kidney failure. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic disease with various cardiac abnormalities. Details on the cardiovascular profile of patients with ADPKD who are undergoing kidney transplantation (KT) and its progression are limited.
    Methods: Echocardiographic data within 2 years before KT (1993-2020), and major adverse cardiovascular events (MACEs) after transplantation were retrieved. The primary outcome is to assess cardiovascular abnormalities on echocardiography at the time of transplantation in ADPKD as compared with patients without ADPKD matched by sex (male, 59.4%) and age at transplantation (57.2 ± 8.8 years).
    Results: Compared with diabetic nephropathy (DN, n = 271) and nondiabetic, patients without ADPKD (NDNA) (n = 271) at the time of KT, patients with ADPKD (n = 271) had lower rates of left ventricular hypertrophy (LVH) (39.4% vs. 66.4% vs. 48.6%), mitral (2.7% vs. 6.3% vs. 7.45) and tricuspid regurgitations (1.8% vs. 6.6% vs. 7.2%). Patients with ADPKD had less diastolic (25.3%) and systolic (5.6%) dysfunction at time of transplantation. Patients with ADPKD had the most favorable post-transplantation survival (median 18.7 years vs. 12.0 for diabetic nephropathy [DN] and 13.8 years for nondiabetic non-ADPKD [NDNA]; P < 0.01) and the most favorable MACE-free survival rate (hazard ratio = 0.51, P < 0.001). Patients with ADPKD had worsening of their valvular function and an increase in the sinus of Valsalva diameter post-transplantation (38.2 vs. 39.9 mm, P < 0.01).
    Conclusion: ADPKD transplant recipients have the most favorable cardiac profile pretransplantation with better patient survival and MACE-free survival rates but worsening valvular function and increasing sinus of Valsalva diameter, as compared with patients with other kidney diseases.
    Keywords:  ADPKD; MACE; cardiovascular outcome; echocardiogram; kidney transplantation; valvular disease
    DOI:  https://doi.org/10.1016/j.ekir.2022.06.006
  10. Intern Med. 2022 ;61(18): 2765-2769
    A Novel Homozygous Variant in GAS2L2 in Two Sisters with Primary Ciliary Dyskinesia.
    Guofei Feng, Yifei Xu, Shun Saso, Hajime Sasano, Shigeto Kondoh, Hidetoshi Itani, Shimpei Gotoh, Mizuho Nagao, Makoto Ikejiri, Masaki Tanabe, Kazuhiko Takeuchi.
      Primary ciliary dyskinesia (PCD) is a rare hereditary disease. We herein report two sisters in their 20s with suspected PCD. They were both born at full term and did not have situs inversus. Chest computed tomography showed similar signs of bronchiectasis in both siblings. Genetic examinations of the family confirmed that the sisters both harbored a homozygous variant in the growth-arrest-specific 2-like 2 (GAS2L2) gene. This is the third report of a family with PCD caused by a GAS2L2 variant.
    Keywords:  GAS2L2; bronchiectasis; gene; primary ciliary dyskinesia; whole-exome sequencing
    DOI:  https://doi.org/10.2169/internalmedicine.8884-21
  11. Biol Cell. 2022 Sep 13.
    The distal central pair segment is structurally specialised and contributes to IFT turnaround and assembly of the tip capping structures in Chlamydomonas flagella.
    Ambra Pratelli, Dalia Corbo, Pietro Lupetti, Caterina Mencarelli.
       BACKGROUND INFORMATION: Cilia and flagella are dynamic organelles whose assembly and maintenance depend on an activetrafficking process known as the IntraFlagellar Transport (IFT), during which trains of IFT protein particles are moved by specific motors and carry flagellar precursors and turnover products along the axoneme. IFT consists of an anterograde (from base to tip) and a retrograde (from tip to base) phase. During IFT turnaround at the flagellar tip, anterograde trains release their cargoes and remodel to form the retrograde trains. Thus, turnaround is crucial for correct IFT. However, current knowledge of its mechanisms is limited.
    RESULTS: We show here that in Chlamydomonas flagella the distal ∼200 nm central pair (CP) segment is structurally differentiated for the presence of a ladder-like structure (LLS). During IFT turnaround, the IFT172 subunit dissociates from the IFT- B protein complex and binds to the LLS-containing CP segment, while the IFT-B complex participates in the assembly of the CP capping structures. The IFT scaffolding function played by the LLS-containing CP segment relies on anchoring components other than the CP microtubules, since IFT turnaround occurs also in the CP-devoid pf18 mutant flagella.
    CONCLUSIONS: During IFT turnaround in Chlamydomonas flagella, i) the LLS and the CP terminal plates act as anchoring platforms for IFT172 and the IFT-B complex, respectively, and ii) during its remodeling, the IFT-B complex contributes to the assembly of the CP capping structures.
    SIGNIFICANCE: Our results indicate that in full length Chlamydomonas flagella IFT remodeling occurs by a specialized mechanism that involves flagellar tip structures and is distinct from the previously proposed model in which the capability to reverse motility would be intrinsic of IFT train and independent by any other flagellar structure.
    Keywords:  IntraFlagellar Transport (IFT); cilia; electron tomography; flagellar tip; immunolabelling
    DOI:  https://doi.org/10.1111/boc.202200038
  12. Life Sci Alliance. 2022 Dec;pii: e202201505. [Epub ahead of print]5(12):
    Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphology.
    Noah Moruzzi, Ismael Valladolid-Acebes, Sukanya A Kannabiran, Sara Bulgaro, Ingo Burtscher, Barbara Leibiger, Ingo B Leibiger, Per-Olof Berggren, Kerstin Brismar.
      Primary cilia have recently emerged as cellular signaling organelles. Their homeostasis and function require a high amount of energy. However, how energy depletion and mitochondria impairment affect cilia have barely been addressed. We first studied the spatial relationship between a mitochondria subset in proximity to the cilium in vitro, finding similar mitochondrial activity measured as mitochondrial membrane potential compared with the cellular network. Next, using common primary cilia cell models and inhibitors of mitochondrial energy production, we found alterations in cilia number and/or length due to energy depletion and mitochondrial reactive oxygen species (ROS) overproduction. Finally, by using a mouse model of type 2 diabetes mellitus, we provided in vivo evidence that cilia morphology is impaired in diabetic nephropathy, which is characterized by ROS overproduction and impaired mitochondrial metabolism. In conclusion, we showed that energy imbalance and mitochondrial ROS affect cilia morphology and number, indicating that conditions characterized by mitochondria and radicals imbalances might lead to ciliary impairment.
    DOI:  https://doi.org/10.26508/lsa.202201505
  13. Front Physiol. 2022 ;13 917510
    Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif.
    Liang Wang, Yahui Lu, Guanhui Cai, Hongyu Chen, Gen Li, Luwei Liu, Lian Sun, Zhaolan Guan, Wen Sun, Chunyang Zhao, Hua Wang.
      Human adipose-derived stem cells (hASCs) have multi-directional differentiation potential including osteogenic differentiation. Mechanical stimulation is thought to be a key regulator of bone remodeling and has been proved to promote osteogenic differentiation of mesenchymal stem cells. However, the mechanism how mechanical tension-induced osteogenesis of hASCs still remains poor understood. Polycystin-2 (PC2), a member of the transient receptor potential polycystic (TRPP) family, is involved in cilia-mediated mechanical transduction. To understand the role of PC2 in osteogenic differentiation under mechanical stimuli in hASCs, PKD2 gene was stably silenced by using lentivirus-mediated shRNA technology. The results showed that mechanical tension sufficiently enhanced osteogenic differentiation but hardly affected proliferation of hASCs. Silencing PKD2 gene caused hASCs to lose the ability of sensing mechanical stimuli and subsequently promoting osteogenesis. PC2 knock-out also reduced the cilia population frequency and cilia length in hASCs. TAZ (transcriptional coactivator with PDZ-binding motif, also known as Wwtr1) could mediate the genes regulation and biological functions of mechanotransduction signal pathway. Here, mechanical tension also enhanced TAZ nuclear translocation of hASCs. PC2 knock-out blocked tension-induced upregulation of nuclear TAZ and suppress tension-induced osteogenesis. TAZ could directly interact with Runx2, and inhibiting TAZ could suppress tension-induced upregulation of Runx2 expression. In summary, our findings demonstrated that PC2 mediate mechanical tension-induced osteogenic differentiation of hASCs by activating TAZ.
    Keywords:  TAZ (transcriptional co-activator with PDZ-binding motif); human adipose-derived stem cells; mechanical stimuli; osteogenesis; polycystin-2
    DOI:  https://doi.org/10.3389/fphys.2022.917510
  14. EMBO J. 2022 Sep 12. e104582
    Bld10p/Cep135 determines the number of triplets in the centriole independently of the cartwheel.
    Akira Noga, Mao Horii, Yumi Goto, Kiminori Toyooka, Takashi Ishikawa, Masafumi Hirono.
      The conserved nine-fold structural symmetry of the centriole is thought to be generated by cooperation between two mechanisms, one dependent on and the other independent of the cartwheel, a sub-centriolar structure consisting of a hub and nine spokes. However, the molecular entity of the cartwheel-independent mechanism has not been elucidated. Here, using Chlamydomonas reinhardtii mutants, we show that Bld10p/Cep135, a conserved centriolar protein that connects cartwheel spokes and triplet microtubules, plays a central role in this mechanism. Using immunoelectron microscopy, we localized hemagglutinin epitopes attached to distinct regions of Bld10p along two lines that connect adjacent triplets. Consistently, conventional and cryo-electron microscopy identified crosslinking structures at the same positions. In centrioles formed in the absence of the cartwheel, truncated Bld10p was found to significantly reduce the inter-triplet distance and frequently form eight-microtubule centrioles. These results suggest that the newly identified crosslinks are comprised of part of Bld10p/Cep135. We propose that Bld10p determines the inter-triplet distance in the centriole and thereby regulates the number of triplets in a cartwheel-independent manner.
    Keywords:  SAS-6; basal body; cilia; flagella; microtubule
    DOI:  https://doi.org/10.15252/embj.2020104582
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