Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects
| العنوان: | Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects |
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| المؤلفون: | Paul T. Conduit, Chisato Tsuji, Fred Bernard, Antoine Guichet, Alice Egerton, Corinne A. Tovey |
| المساهمون: | Institut Jacques Monod (IJM (UMR_7592)), Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), University of Cambridge [UK] (CAM), Conduit, Paul, Tovey, Corinne A [0000-0001-8336-1482], Tsuji, Chisato [0000-0003-3345-3519], Egerton, Alice [0000-0002-6746-2504], Guichet, Antoine [0000-0001-7216-1944], de la Roche, Marc [0000-0002-3757-082X], Conduit, Paul T [0000-0002-7822-1191], Apollo - University of Cambridge Repository, Department of Zoology [Cambridge], Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Department of Biochemistry [Cambridge] |
| المصدر: | Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, 2021, 220 (8), ⟨10.1083/jcb.202010020⟩ The Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, In press Tovey, C A, Tsuji, C, Egerton, A, Bernard, F, Guichet, A, Roche, M D L & Conduit, P T 2021, ' Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects ', Journal of Cell Biology, vol. 220, no. 8, e202010020 . https://doi.org/10.1083/jcb.202010020Test |
| بيانات النشر: | Apollo - University of Cambridge Repository, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Cell division, [SDV]Life Sciences [q-bio], Cell Cycle Proteins, Biochemistry, Microtubules, Animals, Genetically Modified, 0302 clinical medicine, Drosophila Proteins, Phosphorylation, Cytoskeleton, 0303 health sciences, Microscopy, Confocal, biology, Chemistry, Cell biology, Drosophila melanogaster, Female, Microtubule-Associated Proteins, Cell Division, Protein Binding, Gene isoform, Nerve Tissue Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Development, Article, 03 medical and health sciences, Structure-Activity Relationship, Microtubule, Animals, Humans, Cell cycle and division, Protein Interaction Domains and Motifs, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Microtubule nucleation, Homeodomain Proteins, CDK5RAP2, Cell growth, Cell Biology, Cytosol, Tubulin, Fertility, HEK293 Cells, Microscopy, Fluorescence, Centrosome, biology.protein, 030217 neurology & neurosurgery, Cell Cycle and Division |
| الوصف: | We show that autoinhibition regulates the binding between microtubule nucleating complexes and proteins that tether them to sites of microtubule nucleation. Failure to regulate this binding properly can lead to ectopic cytosolic microtubule nucleation and major defects during cell division. γ-Tubulin ring complexes (γ-TuRCs) nucleate microtubules. They are recruited to centrosomes in dividing cells via binding to N-terminal CM1 domains within γ-TuRC–tethering proteins, including Drosophila Centrosomin (Cnn). Binding promotes microtubule nucleation and is restricted to centrosomes in dividing cells, but the mechanism regulating binding remains unknown. Here, we identify an extreme N-terminal CM1 autoinhibition (CAI) domain found specifically within the centrosomal isoform of Cnn (Cnn-C) that inhibits γ-TuRC binding. Robust binding occurs after removal of the CAI domain or with the addition of phosphomimetic mutations, suggesting that phosphorylation helps relieve inhibition. We show that regulation of Cnn binding to γ-TuRCs is isoform specific and that misregulation of binding can result in ectopic cytosolic microtubules and major defects during cell division. We also find that human CDK5RAP2 is autoinhibited from binding γ-TuRCs, suggesting conservation across species. Overall, our results shed light on how and why CM1 domain binding to γ-TuRCs is regulated. |
| وصف الملف: | application/pdf |
| تدمد: | 0021-9525 1540-8140 |
| DOI: | 10.17863/cam.71918 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc01f7f32c694795f0b9249c698ca2cdTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fc01f7f32c694795f0b9249c698ca2cd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219525 15408140 |
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| DOI: | 10.17863/cam.71918 |