bims-bicyki Biomed News
on Bicaudal-C1 and interactors in cystic kidney disease
Issue of 2023‒05‒07
thirteen papers selected by
Céline Gagnieux
École Polytechnique Fédérale de Lausanne (EPFL)
  1. Polycystin-2, mechanosensing, and left-right asymmetry in autosomal dominant polycystic kidney disease.
  2. Primary cilia shape hallmarks of health and aging.
  3. Kidney Transplantation After Renal Transcatheter Arterial Embolization for Cyst Infection in a Hemodialysis Patient With Autosomal Dominant Polycystic Kidney Disease: A Case Report.
  4. Metabolomic Profiling to Identify Early Urinary Biomarkers and Metabolic Pathway Alterations in Autosomal Dominant Polycystic Kidney Disease.
  5. Barriers and facilitators to the transplant process among patients living with polycystic kidney disease: a qualitative Approach.
  6. A Case Report of Successful Kidney Transplantation in a Patient With Autosomal Dominant Polycystic Kidney Disease Who Underwent Thoracic Endovascular Aortic Repair for Type B Aortic Dissection.
  7. Unruptured untreated intracranial aneurysms: a retrospective analysis of outcomes of 445 aneurysms managed conservatively.
  8. The cilium-centrosome axis in coupling cell cycle exit and cell fate.
  9. Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti.
  10. Ordered deployment of distinct ciliary beating machines in growing axonemes of vertebrate multiciliated cells.
  11. Quantum noise may limit the mechanosensory sensitivity of cilia in the left-right organizer of the vertebrate bodyplan.
  12. Outer Arm Dynein Light Chain LC1 Is Required for Normal Motor Assembly Kinetics, Ciliary Stability and Motility.
  13. Cilia-Derived Extracellular Vesicles in Caenorhabditis Elegans: In Vivo Imaging and Quantification of Extracellular Vesicle Release and Capture.
  1. Kidney Int. 2023 Apr 26. pii: S0085-2538(23)00233-8. [Epub ahead of print]
    Polycystin-2, mechanosensing, and left-right asymmetry in autosomal dominant polycystic kidney disease.
    Zhiyong Chen, Iain A Drummond.
      
    Keywords:  calcium signaling; left-right organizer; optical deflection; primary cilia; zebrafish embryos
    DOI:  https://doi.org/10.1016/j.kint.2023.03.023
  2. Trends Mol Med. 2023 May 01. pii: S1471-4914(23)00071-0. [Epub ahead of print]
    Primary cilia shape hallmarks of health and aging.
    Diana Filipa Silva, Cláudia Cavadas.
      Primary cilia are specialized organelles that sense changes in extracellular milieu, and their malfunction is responsible for several disorders (ciliopathies). Increasing evidence shows that primary cilia regulate tissue and cellular aging related features, which led us to review the evidence on their role in potentiating and/or accelerating the aging process. Primary cilia malfunction is associated with some age-related disorders, from cancer to neurodegenerative and metabolic disorders. However, there is limited understanding of molecular pathways underlying primary cilia dysfunction, resulting in scarce ciliary-targeted therapies available. Here, we discuss the findings on primary cilia dysfunction as modulators of the health and aging hallmarks, and the pertinence of ciliary pharmacological targeting to promote healthy aging or treat age-related diseases.
    Keywords:  ciliary-targeted pharmacological approaches; hallmarks of aging; hallmarks of health; primary cilia
    DOI:  https://doi.org/10.1016/j.molmed.2023.04.001
  3. Transplant Proc. 2023 Apr 28. pii: S0041-1345(23)00228-2. [Epub ahead of print]
    Kidney Transplantation After Renal Transcatheter Arterial Embolization for Cyst Infection in a Hemodialysis Patient With Autosomal Dominant Polycystic Kidney Disease: A Case Report.
    Keiko Iguchi, Tomoaki Iwai, Akihiro Kosoku, Shunji Nishide, Kazuya Kabei, Norihiro Kumada, Junji Uchida.
      A 31-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) required antibiotic therapy for repeated renal cyst infections. The patient was scheduled for a living donor renal transplant with her mother as the donor. Two months before surgery, the patient was admitted to the hospital due to a severe renal cyst infection that improved with antibiotic treatment and percutaneous drainage, but the scheduled surgery was postponed. Transcatheter arterial embolization (TAE) was performed to control repeated renal cyst infections. Seven months after TAE, the patient underwent living donor renal transplantation. The postoperative course was uneventful, and the patient was discharged from the hospital on immunosuppressive medication 26 days after surgery with no evidence of recurrent infection or deterioration of renal function. Thirty months after transplantation, there has been no recurrence of infection.
    DOI:  https://doi.org/10.1016/j.transproceed.2023.03.055
  4. Am J Physiol Renal Physiol. 2023 May 04.
    Metabolomic Profiling to Identify Early Urinary Biomarkers and Metabolic Pathway Alterations in Autosomal Dominant Polycystic Kidney Disease.
    Eden A Houske, Matthew G Glimm, Annika R Bergstrom, Sally K Slipher, Hope D Welhaven, Mark C Greenwood, Greta M Linse, Ronald K June, Alan S L Yu, Darren P Wallace, Alyssa K Hahn.
      Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of numerous fluid-filled cysts that lead to progressive loss of functional nephrons. Currently, there is an unmet need for diagnostic and prognostic indicators of early-stage ADPKD. Metabolites were extracted from the urine of early-stage ADPKD patients (n=48) and age- and sex-matched normal controls (n=47) and analyzed by liquid chromatography-mass spectrometry. Orthogonal partial least squares-discriminant analysis was employed to generate a global metabolomic profile of early ADPKD for the identification of metabolic pathway alterations and discriminatory metabolites as candidate diagnostic and prognostic biomarkers. The global metabolomic profile exhibited alterations in metabolism of steroids, fatty acids, pyruvate, amino acids, and the urea cycle. A panel of 46 metabolite features were identified as candidate diagnostic biomarkers. Notable putative identities of candidate diagnostic biomarkers for early detection include creatinine, cAMP, dCMP, various androgens, betaine aldehyde, phosphoric acid, choline, 18-hydroxycorticosterone, and cortisol. Metabolic pathways associated with variable rates of disease progression included metabolism of steroids, vitamin D3, fatty acids, amino acids, sialic acid, the pentose phosphate pathway, the tricarboxylic acid cycle, and chondroitin sulfate and heparin sulfate degradation. A panel of 41 metabolite features were identified as candidate prognostic biomarkers. Notable putative identities of candidate prognostic biomarkers include ethanolamine, C20:4 anandamide phosphate, progesterone, various androgens, betaine aldehyde, inflammatory lipids, and choline. Our exploratory data support metabolic reprogramming in early ADPKD and demonstrate the ability of mass spectrometry-based global metabolomic profiling to detect metabolic pathway alterations as new therapeutic targets and biomarkers of ADPKD.
    Keywords:  biomarkers; liquid chromatography-mass spectrometry; metabolomics; polycystic kidney disease; urine
    DOI:  https://doi.org/10.1152/ajprenal.00301.2022
  5. BMC Nephrol. 2023 May 01. 24(1): 119
    Barriers and facilitators to the transplant process among patients living with polycystic kidney disease: a qualitative Approach.
    Juliana Smith, Orlando O Harris, Deborah Adey, Meyeon Park.
      BACKGROUND: Kidney transplant is the gold standard for renal replacement therapy in patients with autosomal dominant polycystic kidney disease (ADPKD), which is the fourth leading cause of kidney failure. Despite the medical and economic benefits of preemptive kidney transplant over dialysis before transplant, only 9-21% of qualifying patients receive preemptive transplants. Given the low rates of preemptive transplant, the aim of this study was to determine perceived facilitators and barriers to preemptive transplant among ADPKD patients using a qualitative approach.METHODS: Data were collected between July 2021 and January 2022 from virtual individual semi-structured interviews of 16 adult participants with ADPKD. Qualitative analysis of the recorded interviews was conducted to generate themes.
    RESULTS: Our findings revealed two themes specific for facilitators to preemptive transplant (social support and patient agency) and three themes specific to barriers for preemptive transplant (inadequate social support, gaps in knowledge, and institutional and systemic policies). The results also include various subthemes and the application of these themes to the social ecological model.
    CONCLUSIONS: These findings suggest that increasing social support and patient agency, such as through patient navigator programs and encouraging effective communication between health care providers and patients, can facilitate the transplant process. Increasing dissemination of transplant knowledge from institutions and systems to patients through paired kidney exchange education and live donor outreach can also increase timely access to preemptive kidney transplants for patients with ADPKD. Our findings are limited by our single site study in the US, which may not apply to individuals experiencing different social, cultural, and health access conditions.
    Keywords:  ADPKD; Kidney transplant; PKD; Polycystic kidney disease; Preemptive transplant; Transplant patient perspective
    DOI:  https://doi.org/10.1186/s12882-023-03174-6
  6. Transplant Proc. 2023 Apr 27. pii: S0041-1345(23)00131-8. [Epub ahead of print]
    A Case Report of Successful Kidney Transplantation in a Patient With Autosomal Dominant Polycystic Kidney Disease Who Underwent Thoracic Endovascular Aortic Repair for Type B Aortic Dissection.
    Kiyoshi Setoguchi, Tadahiko Tokumoto, Erika Ikezoe, Hiroki Tsujioka, Minoru Inoue, Asumi Nirazuka, Kintaro Hasegawa, Yuka Yasuda, Akiyoshi Osaka, Yasuyuki Inoe, Akinori Nakayama, Hiroki Shirakawa, Tetsuro Takeda, Kazutaka Saito.
      BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with several cardiovascular disorders, including aortic dissection, which preferentially occurs at the thoracic or abdominal level. Because there are few case reports describing surgical repair for aortic dissection followed by renal transplantation in patients with ADPKD, kidney transplantation performed after repair for aortic dissection remains challenging.CASE PRESENTATION: A 34-year-old Japanese man with end-stage renal disease secondary to ADPKD underwent thoracic endovascular aortic repair for complicated acute type B aortic dissection 12 months earlier. A contrast computed tomography scan before transplantation revealed an aortic dissection involving the descending aorta proximal to the common iliac arteries and confirmed multiple large bilateral renal cysts. After simultaneous right native nephrectomy, the patient underwent preemptive living-donor kidney transplantation obtained from his mother. Intraoperatively, we noted that dissection of the external iliac vessels was difficult because of dense adhesions. Arterial clamping was performed immediately below the bifurcation of the internal iliac artery to prevent further aortic dissection of the external iliac artery. After end-to-end anastomosis to the internal iliac artery was completed and the vascular clamp was released, the kidney began to produce urine immediately.
    CONCLUSION: This case suggests that kidney transplantation in patients undergoing endovascular aortic repair for aortic dissection can be performed by adequately applying a vascular clamp proximal to the internal iliac artery during vascular anastomosis.
    DOI:  https://doi.org/10.1016/j.transproceed.2023.03.032
  7. Br J Neurosurg. 2023 May 05. 1-9
    Unruptured untreated intracranial aneurysms: a retrospective analysis of outcomes of 445 aneurysms managed conservatively.
    Robert J Spencer, Edward J St George.
      BACKGROUND: Factors predicting the growth or rupture of unruptured intracranial aneurysms (UIAs) remain under debate. Increased availability of neuro-imaging has led to increasing incidental findings, therefore understanding the natural history is vital to make appropriate management and follow-up decisions. We analysed a large dataset of UIAs to better identify patients at increased risk, therefore requiring enhanced monitoring and/or prophylactic intervention.METHODS: Electronic patient records were reviewed from consecutive patients regarding the following data: baseline demographics; past medical and smoking history; indication for imaging detecting the UIA(s); size, location and morphology of UIA(s), duration of imaging follow-up, detection of growth and rupture. Logistic regression was used to identify risk factors for UIA growth or rupture. Subgroup analysis was performed for 'small' aneurysms (<7mm).
    RESULTS: 445 UIAs in 274 patients were analysed. Total imaging follow-up was 2268 aneurysm-years (median 3.8 years/UIA). 27 UIAs grew (1.2% annually), and 15 ruptured (0.46%). 70.1% of UIAs were detected incidentally. Mean aneurysm diameter was 4.1mm.Logistic regression identified age < 50, autosomal dominant polycystic kidney disease (ADPKD), hypertension and diameter > 7mm as significant risk factors for growth/rupture. Additionally, previous smoking compared to current smoking was a protective factor against growth or rupture, but no significant difference was seen when comparing current- with non-smokers. Small aneurysm subgroup analysis identified diameter > 5mm, age < 50, ADPKD, and ongoing smoking as risk factors. No significant difference was observed in risk between those with and without previous SAH.
    CONCLUSIONS: This study underlines the need for imaging surveillance of even small UIAs. Smoking is a modifiable risk factor for growth/rupture of pre-existing aneurysms, while ADPKD is a particularly strong risk factor.
    Keywords:  (Alphabetised): Subarachnoid Haemorrhage; surveillance study; unruptured intracranial aneurysm
    DOI:  https://doi.org/10.1080/02688697.2023.2207646
  8. J Cell Sci. 2023 May 01. pii: jcs260454. [Epub ahead of print]136(9):
    The cilium-centrosome axis in coupling cell cycle exit and cell fate.
    Priti S Atmakuru, Jyotsna Dhawan.
      The centrosome is an evolutionarily conserved, ancient organelle whose role in cell division was first described over a century ago. The structure and function of the centrosome as a microtubule-organizing center, and of its extracellular extension - the primary cilium - as a sensory antenna, have since been extensively studied, but the role of the cilium-centrosome axis in cell fate is still emerging. In this Opinion piece, we view cellular quiescence and tissue homeostasis from the vantage point of the cilium-centrosome axis. We focus on a less explored role in the choice between distinct forms of mitotic arrest - reversible quiescence and terminal differentiation, which play distinct roles in tissue homeostasis. We outline evidence implicating the centrosome-basal body switch in stem cell function, including how the cilium-centrosome complex regulates reversible versus irreversible arrest in adult skeletal muscle progenitors. We then highlight exciting new findings in other quiescent cell types that suggest signal-dependent coupling of nuclear and cytoplasmic events to the centrosome-basal body switch. Finally, we propose a framework for involvement of this axis in mitotically inactive cells and identify future avenues for understanding how the cilium-centrosome axis impacts central decisions in tissue homeostasis.
    Keywords:  Cell cycle; Cell fate; Centrosome; Differentiation; Muscle stem cells; Primary cilium; Quiescence; RNA
    DOI:  https://doi.org/10.1242/jcs.260454
  9. Front Neurosci. 2023 ;17 1162937
    Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti.
    Laura A Lindner, Dennis Derstroff, Dominik Oliver, Katrin Reimann.
      Tubby-like proteins are membrane-associated adaptors that mediate directional trafficking into primary cilia. In inner ear sensory epithelia, cilia-including the hair cell's kinocilium-play important roles as organizers of polarity, tissue architecture and cellular function. However, auditory dysfunction in tubby mutant mice was recently found to be related to a non-ciliary function of tubby, the organization of a protein complex in sensory hair bundles of auditory outer hair cells (OHCs). Targeting of signaling components into cilia in the cochlea might therefore rather rely on closely related tubby-like proteins (TULPs). In this study, we compared cellular and subcellular localization of tubby and TULP3 in the mouse inner ear sensory organs. Immunofluorescence microscopy confirmed the previously reported highly selective localization of tubby in the stereocilia tips of OHCs and revealed a previously unnoticed transient localization to kinocilia during early postnatal development. TULP3 was detected in the organ of Corti and vestibular sensory epithelium, where it displayed a complex spatiotemporal pattern. TULP3 localized to kinocilia of cochlear and vestibular hair cells in early postnatal development but disappeared subsequently before the onset of hearing. This pattern suggested a role in targeting ciliary components into kinocilia, possibly related to the developmental processes that shape the sensory epithelia. Concurrent with loss from kinocilia, pronounced TULP3 immunolabeling progressively appeared at microtubule bundles in non-sensory Pillar (PCs) and Deiters cells (DC). This subcellular localization may indicate a novel function of TULP proteins associated with the formation or regulation of microtubule-based cellular structures.
    Keywords:  TULP3; hair cells; immunohistochemistry; organ of Corti; phosphoinositides; tubby
    DOI:  https://doi.org/10.3389/fnins.2023.1162937
  10. Differentiation. 2023 Apr 13. pii: S0301-4681(23)00020-8. [Epub ahead of print]131 49-58
    Ordered deployment of distinct ciliary beating machines in growing axonemes of vertebrate multiciliated cells.
    Chanjae Lee, Yun Ma, Fan Tu, John B Wallingford.
      The beating of motile cilia requires the coordinated action of diverse machineries that include not only the axonemal dynein arms, but also the central apparatus, the radial spokes, and the microtubule inner proteins. These machines exhibit complex radial and proximodistal patterns in mature axonemes, but little is known about the interplay between them during motile ciliogenesis. Here, we describe and quantify the relative rates of axonemal deployment for these diverse cilia beating machineries during the final stages of differentiation of Xenopus epidermal multiciliated cells.
    DOI:  https://doi.org/10.1016/j.diff.2023.03.001
  11. Prog Biophys Mol Biol. 2023 May 01. pii: S0079-6107(23)00044-5. [Epub ahead of print]
    Quantum noise may limit the mechanosensory sensitivity of cilia in the left-right organizer of the vertebrate bodyplan.
    Julyan H E Cartwright.
      Could nature be harnessing quantum mechanics in cilia to optimize the sensitivity of the mechanism of left-right symmetry breaking during development in vertebrates? I evaluate whether mechanosensing - i.e., the detection of a left-right asymmetric signal through mechanical stimulation of sensory cilia, as opposed to biochemical signalling - might be functioning in the embryonic left-right organizer of the vertebrate bodyplan through quantum mechanics. I conclude that there is a possible role for quantum biology in mechanosensing in cilia. The system may not be limited by classical thermal noise, but instead by quantum noise, with an amplification process providing active cooling.
    Keywords:  Left–right organizer; Mechanosensing; Quantum biology; Symmetry breaking; cilia
    DOI:  https://doi.org/10.1016/j.pbiomolbio.2023.04.010
  12. Mol Biol Cell. 2023 May 03. mbcE23030104
    Outer Arm Dynein Light Chain LC1 Is Required for Normal Motor Assembly Kinetics, Ciliary Stability and Motility.
    Miho Sakato-Antoku, Stephen M King.
      Light chain 1 (LC1) is a highly conserved leucine-rich repeat protein associated with the microtubule-binding domain of the Chlamydomonas outer dynein arm γ heavy chain. LC1 mutations in humans and trypanosomes lead to motility defects while its loss in oomycetes results in aciliate zoospores. Here we describe a Chlamydomonas LC1 null mutant (dlu1-1). This strain has reduced swimming velocity and beat frequency, can undergo waveform conversion but often exhibits loss of hydrodynamic coupling between the cilia. Following deciliation, Chlamydomonas cells rapidly rebuild cytoplasmic stocks of axonemal dyneins. Loss of LC1 disrupts the kinetics of this cytoplasmic preassembly such that most outer arm dynein heavy chains remain monomeric even after several hours. This suggests that association of LC1 with its heavy chain-binding site is a key step or checkpoint in the outer arm dynein assembly process. Similar to strains lacking the entire outer arm and inner arm I1/f, we found that loss of LC1 and I1/f in dlu1-1 ida1 double mutants resulted in cells unable to build cilia under normal conditions. Furthermore, dlu1-1 cells do not exhibit the usual ciliary extension in response to lithium treatment. Together, these observations suggest that LC1 plays an important role in the maintenance of axonemal stability. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].
    DOI:  https://doi.org/10.1091/mbc.E23-03-0104
  13. Methods Mol Biol. 2023 ;2668 277-299
    Cilia-Derived Extracellular Vesicles in Caenorhabditis Elegans: In Vivo Imaging and Quantification of Extracellular Vesicle Release and Capture.
    Adrià Razzauti, Teresa Lobo, Patrick Laurent.
      Caenorhabditis elegans is a microscopic model nematode characterized by body transparency and ease of genetic manipulation. Release of extracellular vesicles (EVs) is observed from different tissues; of particular interest are the EVs released by the cilia of sensory neurons. C. elegans ciliated sensory neurons produce EVs that are environmentally released and/or captured by neighboring glial cells. In this chapter, we describe a methodological approach to image the biogenesis, release, and capture of EVs by glial cells in anesthetized animals. This method will allow the experimenter to visualize and quantify the release of ciliary-derived EVs.
    Keywords:  Caenorhabditis elegans; Ciliary-derived EVs; EV capture; Ectosomes; In vivo imaging; Intercellular communication
    DOI:  https://doi.org/10.1007/978-1-0716-3203-1_19
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