Ninein is essential for apico-basal microtubule formation and CLIP-170 facilitates its redeployment to non-centrosomal microtubule organizing centres
| العنوان: | Ninein is essential for apico-basal microtubule formation and CLIP-170 facilitates its redeployment to non-centrosomal microtubule organizing centres |
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| المؤلفون: | James Perkins, Benjamin J. Tyrrell, Jonathan R Gadsby, Elizabeth K. Lund, Mette M. Mogensen, Deborah A. Goldspink, Paul Thomas, Thomas Wileman, Chris Rookyard, Niels Galjart |
| المساهمون: | Cell biology, Gadsby, Jonathan [0000-0001-7986-4917], Mogensen, Mette M [0000-0002-8965-1592], Apollo - University of Cambridge Repository |
| المصدر: | Open Biology, 7(2):160274. The Royal Society Open Biology, Vol 7, Iss 2 (2017) Open Biology |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, non-centrosomal mtocs, Microtubule-associated protein, clip-170, Immunology, RAC1, Biology, General Biochemistry, Genetics and Molecular Biology, Cell Line, Madin Darby Canine Kidney Cells, microtubules, 03 medical and health sciences, Gene Knockout Techniques, Mice, 0302 clinical medicine, Dogs, Microtubule, Cell polarity, Animals, Humans, Cytoskeleton, Cell Shape, lcsh:QH301-705.5, Microtubule nucleation, iqgap1, rac1, Research, General Neuroscience, ninein, Cell Polarity, Microtubule organizing center, Cell Differentiation, Epithelial Cells, Cell biology, Neoplasm Proteins, Cytoskeletal Proteins, 030104 developmental biology, lcsh:Biology (General), Centrosome, Microtubule-Associated Proteins, 030217 neurology & neurosurgery, Microtubule-Organizing Center, Research Article |
| الوصف: | Differentiation of columnar epithelial cells involves a dramatic reorganization of the microtubules (MTs) and centrosomal components into an apico-basal array no longer anchored at the centrosome. Instead, the minus-ends of the MTs become anchored at apical non-centrosomal microtubule organizing centres (n-MTOCs). Formation of n-MTOCs is critical as they determine the spatial organization of MTs, which in turn influences cell shape and function. However, how they are formed is poorly understood. We have previously shown that the centrosomal anchoring protein ninein is released from the centrosome, moves in a microtubule-dependent manner and accumulates at n-MTOCs during epithelial differentiation. Here, we report using depletion and knockout (KO) approaches that ninein expression is essential for apico-basal array formation and epithelial elongation and that CLIP-170 is required for its redeployment to n-MTOCs. Functional inhibition also revealed that IQGAP1 and active Rac1 coordinate with CLIP-170 to facilitate microtubule plus-end cortical targeting and ninein redeployment. Intestinal tissue andin vitroorganoids from theClip1/Clip2double KO mouse with deletions in the genes encoding CLIP-170 and CLIP-115, respectively, confirmed requirement of CLIP-170 for ninein recruitment to n-MTOCs, with possible compensation by other anchoring factors such as p150Gluedand CAMSAP2 ensuring apico-basal microtubule formation despite loss of ninein at n-MTOCs. |
| وصف الملف: | application/pdf |
| تدمد: | 2046-2441 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cac5d8a751eedf1515224312d438ab11Test https://pure.eur.nl/en/publications/9ccb74b3-bbca-47a8-9977-7f95f4f1e2b5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cac5d8a751eedf1515224312d438ab11 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20462441 |
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