In eukaryotes, two sources of Ca are accessed to allow rapid changes in the cytosolic levels of this second messenger: the extracellular medium and intracellular Ca stores, such as the endoplasmic reticulum. One class of channel that permits Ca entry is the transient receptor potential (TRP) superfamily, including the polycystic kidney disease (PKD) proteins, or polycystins. Channels that release Ca from intracellular stores include the inositol 1,4,5-trisphosphate/ryanodine receptor (ITPR/RyR) superfamily. Here, we characterise a family of proteins that are only encoded by oomycete genomes, that we have named PKDRR, since they share domains with both PKD and RyR channels. We provide evidence that these proteins belong to the TRP superfamily and are distinct from the ITPR/RyR superfamily in terms of their evolutionary relationships, protein domain architectures and predicted ion channel structures. We also demonstrate that a hypothetical PKDRR protein from is produced by this organism, is located in the cell-surface membrane and forms multimeric protein complexes. Efforts to functionally characterise this protein in a heterologous expression system were unsuccessful but support a cell-surface localisation. These PKDRR proteins represent potential targets for the development of new "fungicides", since they are of a distinctive structure that is only found in oomycetes and not in any other cellular organisms.
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http://dx.doi.org/10.3390/pathogens9070577 | DOI Listing |
Genes (Basel)
December 2024
The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy.
: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is mainly characterized by renal involvement with progressive bilateral development of renal cysts and volumetric increase in the kidneys, causing a loss of renal function, chronic kidney disease (CKD), and kidney failure. The occurrence of mosaicism may modulate the clinical course of the disease. Mosaicism is characterized by a few cell populations with different genomes.
View Article and Find Full Text PDFStem Cell Reports
January 2025
Department of Medicine, Division of Nephrology, Institute for Stem Cell & Regenerative Medicine, and Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Plurexa LLC, Seattle, WA 98109, USA. Electronic address:
The mammalian target of rapamycin (mTOR) pathway is a therapeutic target in polycystic kidney disease (PKD), but mTOR inhibitors such as everolimus have failed to show efficacy at tolerated doses in clinical trials. Here, we introduce AV457, a novel rapalog developed to reduce side effects, and assess its dose-dependent safety and efficacy versus everolimus in PKD1 and PKD2 human kidney organoids, which form cysts in a PKD-specific way. Both AV457 and everolimus reduce cyst growth over time.
View Article and Find Full Text PDFEur Heart J Imaging Methods Pract
January 2025
Department of Cardiology, Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel, Basel, Switzerland.
Int J Cardiovasc Imaging
January 2025
Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece.
The term acute aortic syndrome (AAS) refers to a range of different entities, including dissection, intramural haematoma and penetrating atherosclerotic ulcer. Patients with chronic renal disease and particularly those with dominant polycystic kidney disease are susceptible to this pathology, given the underlying renal arteriopathy and hypertension. Imaging plays a crucial role in diagnosing, grading and guiding management of these patients, with computed tomography angiography (CTA) being on the frontline.
View Article and Find Full Text PDFNephrol Dial Transplant
January 2025
Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
A substantial number of patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) undergo a nephrectomy, especially in work-up for a kidney transplantation. Currently, there is no evidence-based algorithm to guide clinicians which patients should undergo nephrectomy, the optimal timing of this procedure, or the preferred surgical technique. This systematic review-based consensus statement aimed to answer important questions regarding nephrectomy in ADPKD.
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