CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels
| Autor: | Jens S. Andersen, Mathieu Quinodoz, Reem Suleiman, Pernille Martens, Konstantinos Nikopoulos, André Brás Gonçalves, Pietro Farinelli, Carlo Rivolta, Catja Weiss, Sebastian Patzke, Beinta Biskopstø Joensen, Lotte B. Pedersen, Magnus Per Damsø Jeppesen, Sarah Kirstine Hasselbalch, Søren T. Christensen, Signe Krogh Ohlsen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
Science Cell Cycle Proteins Biology medicine.disease_cause Interactome General Biochemistry Genetics and Molecular Biology Gene Knockout Techniques Ubiquitin Ciliogenesis ubiquitin medicine CEP78 Humans CP110 Biology (General) Mutation General Immunology and Microbiology General Neuroscience Cilium cilia Ubiquitination Nuclear Proteins Cell Biology General Medicine Phosphoproteins Cell biology Ubiquitin ligase centrosome CEP350 Centrosome Microtubule Proteins biology.protein Medicine Microtubule-Associated Proteins Biogenesis Research Article Human |
| Zdroj: | Gonçalves, A B, Hasselbalch, S K, Joensen, B B, Patzke, S, Martens, P, Ohlsen, S K, Quinodoz, M, Nikopoulos, K, Suleiman, R, Jeppesen, M P D, Weiss, C, Christensen, S T, Rivolta, C, Andersen, J S, Farinelli, P & Pedersen, L B 2021, ' CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels ', eLife, vol. 10, e63731 . https://doi.org/10.7554/eLife.63731 eLife eLife, Vol 10 (2021) Gonçalves, A B, Hasselbalch, S K, Joensen, B B, Patzke, S, Martens, P, Ohlsen, S K, Quinodoz, M, Nikopoulos, K, Suleiman, R, Jeppesen, M P D, Weiss, C, Christensen, S T, Rivolta, C, Andersen, J S, Farinelli, P & Pedersen, L B 2021, ' CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels ', eLife, vol. 10, e63731 . https://doi.org/10.7554/elife.63731 |
| DOI: | 10.7554/eLife.63731 |
| Popis: | CEP78 is a centrosomal protein implicated in ciliogenesis and ciliary length control, and mutations in the CEP78 gene cause retinal cone-rod dystrophy associated with hearing loss. However, the mechanism by which CEP78 affects cilia formation is unknown. Based on a recently discovered disease-causing CEP78 p.L150S mutation, we identified the disease-relevant interactome of CEP78. We confirmed that CEP78 interacts with the EDD1-DYRK2-DDB1VPRBP E3 ubiquitin ligase complex, which is involved in CP110 ubiquitination and degradation, and identified a novel interaction between CEP78 and CEP350 that is weakened by the CEP78L150S mutation. We show that CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn leads to centrosomal recruitment of EDD1. Consistently, cells lacking CEP78 display significantly increased cellular and centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restored ciliation frequency to normal. We propose that CEP78 functions downstream of CEP350 to promote ciliogenesis by negatively regulating CP110 levels via an EDD1-dependent mechanism. |
| Databáze: | OpenAIRE |
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