Primary cilia and actin regulatory pathways in renal ciliopathies
Ciliopathies are a group of rare genetic disorders caused by defects to the structure or function of the primary cilium. They often affect multiple organs, leading to brain malformations, congenital heart defects, and anomalies of the retina or skeletal system. Kidney abnormalities are among the mos...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Nephrology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneph.2023.1331847/full |
| _version_ | 1827159015118864384 |
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| author | Rita Kalot Rita Kalot Zachary Sentell Thomas M. Kitzler Thomas M. Kitzler Elena Torban Elena Torban |
| author_facet | Rita Kalot Rita Kalot Zachary Sentell Thomas M. Kitzler Thomas M. Kitzler Elena Torban Elena Torban |
| author_sort | Rita Kalot |
| collection | DOAJ |
| description | Ciliopathies are a group of rare genetic disorders caused by defects to the structure or function of the primary cilium. They often affect multiple organs, leading to brain malformations, congenital heart defects, and anomalies of the retina or skeletal system. Kidney abnormalities are among the most frequent ciliopathic phenotypes manifesting as smaller, dysplastic, and cystic kidneys that are often accompanied by renal fibrosis. Many renal ciliopathies cause chronic kidney disease and often progress to end-stage renal disease, necessitating replacing therapies. There are more than 35 known ciliopathies; each is a rare hereditary condition, yet collectively they account for a significant proportion of chronic kidney disease worldwide. The primary cilium is a tiny microtubule-based organelle at the apex of almost all vertebrate cells. It serves as a “cellular antenna” surveying environment outside the cell and transducing this information inside the cell to trigger multiple signaling responses crucial for tissue morphogenesis and homeostasis. Hundreds of proteins and unique cellular mechanisms are involved in cilia formation. Recent evidence suggests that actin remodeling and regulation at the base of the primary cilium strongly impacts ciliogenesis. In this review, we provide an overview of the structure and function of the primary cilium, focusing on the role of actin cytoskeleton and its regulators in ciliogenesis. We then describe the key clinical, genetic, and molecular aspects of renal ciliopathies. We highlight what is known about actin regulation in the pathogenesis of these diseases with the aim to consider these recent molecular findings as potential therapeutic targets for renal ciliopathies. |
| first_indexed | 2024-03-08T13:50:14Z |
| format | Article |
| id | doaj.art-59fa3abad73f40be8822e82583be5d8d |
| institution | Directory Open Access Journal |
| issn | 2813-0626 |
| language | English |
| last_indexed | 2025-03-20T23:50:24Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nephrology |
| spelling | doaj.art-59fa3abad73f40be8822e82583be5d8d2024-08-03T12:15:17ZengFrontiers Media S.A.Frontiers in Nephrology2813-06262024-01-01310.3389/fneph.2023.13318471331847Primary cilia and actin regulatory pathways in renal ciliopathiesRita Kalot0Rita Kalot1Zachary Sentell2Thomas M. Kitzler3Thomas M. Kitzler4Elena Torban5Elena Torban6Department of Medicine and Department of Physiology, McGill University, Montreal, QC, CanadaThe Research Institute of the McGill University Health Center, Montreal, QC, CanadaDepartment of Human Genetics, McGill University, Montreal, QC, CanadaDepartment of Human Genetics, McGill University, Montreal, QC, CanadaMcGill University Health Center, Montreal, QC, CanadaDepartment of Medicine and Department of Physiology, McGill University, Montreal, QC, CanadaThe Research Institute of the McGill University Health Center, Montreal, QC, CanadaCiliopathies are a group of rare genetic disorders caused by defects to the structure or function of the primary cilium. They often affect multiple organs, leading to brain malformations, congenital heart defects, and anomalies of the retina or skeletal system. Kidney abnormalities are among the most frequent ciliopathic phenotypes manifesting as smaller, dysplastic, and cystic kidneys that are often accompanied by renal fibrosis. Many renal ciliopathies cause chronic kidney disease and often progress to end-stage renal disease, necessitating replacing therapies. There are more than 35 known ciliopathies; each is a rare hereditary condition, yet collectively they account for a significant proportion of chronic kidney disease worldwide. The primary cilium is a tiny microtubule-based organelle at the apex of almost all vertebrate cells. It serves as a “cellular antenna” surveying environment outside the cell and transducing this information inside the cell to trigger multiple signaling responses crucial for tissue morphogenesis and homeostasis. Hundreds of proteins and unique cellular mechanisms are involved in cilia formation. Recent evidence suggests that actin remodeling and regulation at the base of the primary cilium strongly impacts ciliogenesis. In this review, we provide an overview of the structure and function of the primary cilium, focusing on the role of actin cytoskeleton and its regulators in ciliogenesis. We then describe the key clinical, genetic, and molecular aspects of renal ciliopathies. We highlight what is known about actin regulation in the pathogenesis of these diseases with the aim to consider these recent molecular findings as potential therapeutic targets for renal ciliopathies.https://www.frontiersin.org/articles/10.3389/fneph.2023.1331847/fullrenal ciliopathiesgeneticsprimary ciliumciliogenesisactin regulation |
| spellingShingle | Rita Kalot Rita Kalot Zachary Sentell Thomas M. Kitzler Thomas M. Kitzler Elena Torban Elena Torban Primary cilia and actin regulatory pathways in renal ciliopathies Frontiers in Nephrology renal ciliopathies genetics primary cilium ciliogenesis actin regulation |
| title | Primary cilia and actin regulatory pathways in renal ciliopathies |
| title_full | Primary cilia and actin regulatory pathways in renal ciliopathies |
| title_fullStr | Primary cilia and actin regulatory pathways in renal ciliopathies |
| title_full_unstemmed | Primary cilia and actin regulatory pathways in renal ciliopathies |
| title_short | Primary cilia and actin regulatory pathways in renal ciliopathies |
| title_sort | primary cilia and actin regulatory pathways in renal ciliopathies |
| topic | renal ciliopathies genetics primary cilium ciliogenesis actin regulation |
| url | https://www.frontiersin.org/articles/10.3389/fneph.2023.1331847/full |
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