Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disease, which is caused by pathogenic mutations of either PKD1 (85%) or PKD2 (15%) genes, encoding for polycystin-1 (PC1) or polycystin-2 (PC2), respectively. These two proteins hetero-dimerize in renal primary cilia to...

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Format: Online
Language:English
Published: Exon Publications 2024
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Online Access:https://directory.doabooks.org/handle/20.500.12854/136661
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collection Directory of Open Access Books
description Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disease, which is caused by pathogenic mutations of either PKD1 (85%) or PKD2 (15%) genes, encoding for polycystin-1 (PC1) or polycystin-2 (PC2), respectively. These two proteins hetero-dimerize in renal primary cilia to act as a calcium channel. Primary cilia that protrude from cell membranes have a microtubule-based finger-like structure and are found on most mammalian cells. Primary cilia in the kidney have no motility but act as mechanosensors to sense fluid flow through renal tubules. In addition, various signaling proteins related to Hedgehog (Hh) and platelet-derived growth factor receptor alpha (PDGFRα) are localized to the cilia to detect changes in the extracellular environment. Recent studies have demonstrated that many ADPKD animal models have defective cilia in the epithelial cells that line the cysts. Also, animal models targeting ciliary genes show abnormal phenotypes such as polycystic kidneys and developmental defects. These findings reveal that ciliary malfunction is sufficient to cause ADPKD. In this chapter, we will review the putative roles of cilia in cyst formation and development in ADPKD.
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spelling doab-20.500.12854ir-1366612024-05-02T08:19:01Z Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects ADPKD, cilia, ciliopathies, PKD1, PKD2 M Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disease, which is caused by pathogenic mutations of either PKD1 (85%) or PKD2 (15%) genes, encoding for polycystin-1 (PC1) or polycystin-2 (PC2), respectively. These two proteins hetero-dimerize in renal primary cilia to act as a calcium channel. Primary cilia that protrude from cell membranes have a microtubule-based finger-like structure and are found on most mammalian cells. Primary cilia in the kidney have no motility but act as mechanosensors to sense fluid flow through renal tubules. In addition, various signaling proteins related to Hedgehog (Hh) and platelet-derived growth factor receptor alpha (PDGFRα) are localized to the cilia to detect changes in the extracellular environment. Recent studies have demonstrated that many ADPKD animal models have defective cilia in the epithelial cells that line the cysts. Also, animal models targeting ciliary genes show abnormal phenotypes such as polycystic kidneys and developmental defects. These findings reveal that ciliary malfunction is sufficient to cause ADPKD. In this chapter, we will review the putative roles of cilia in cyst formation and development in ADPKD. Published 2024-05-02T08:18:45Z 2024-05-02T08:18:45Z 2015-11-18 chapter 978-0-9944381-0-2 https://directory.doabooks.org/handle/20.500.12854/136661 eng image/jpeg Attribution-NonCommercial-NoDerivatives 4.0 International https://exonpublications.com/index.php/exon/article/view/83 Exon Publications Polycystic Kidney Disease 10.15586/codon.pkd.2015.ch15 10.15586/codon.pkd.2015.ch15 2d6001a3-9e06-4979-bf02-6974e313eb24 01173f6b-d01d-49c3-b18e-93cfe3a0383d 978-0-9944381-0-2 375-396 Brisbane (AU) open access
spellingShingle ADPKD, cilia, ciliopathies, PKD1, PKD2
M
Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects
title Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects
title_full Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects
title_fullStr Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects
title_full_unstemmed Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects
title_short Autosomal Dominant Polycystic Kidney Disease Induced by Ciliary Defects
title_sort autosomal dominant polycystic kidney disease induced by ciliary defects
topic ADPKD, cilia, ciliopathies, PKD1, PKD2
M
topic_facet ADPKD, cilia, ciliopathies, PKD1, PKD2
M
url https://directory.doabooks.org/handle/20.500.12854/136661