Centrosome‐mediated microtubule remodeling during axon formation in human iPSC‐derived neurons
| العنوان: | Centrosome‐mediated microtubule remodeling during axon formation in human iPSC‐derived neurons |
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| المؤلفون: | Lindhout, Feline W., Portegies, Sybren, Kooistra, Robbelien, Herstel, Lotte J., Stucchi, Riccardo, Hummel, Jessica J.A., Scheefhals, Nicky, Katrukha, Eugene A., Altelaar, Maarten, MacGillavry, Harold D., Wierenga, Corette J., Hoogenraad, Casper C., Celbiologie, Biomolecular Mass Spectrometry and Proteomics, Sub Cell Biology, Afd Biomol.Mass Spect. and Proteomics |
| المصدر: | The EMBO Journal EMBO Journal, 40(10), 1. Nature Publishing Group |
| بيانات النشر: | EMBO, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Centriole, Neuroscience(all), Induced Pluripotent Stem Cells, Biology, Biochemistry, Microtubules, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Microtubule, Immunology and Microbiology(all), medicine, hiPSC-derived neuron, Humans, human, Axon, Growth cone, Induced pluripotent stem cell, development, Molecular Biology, 030304 developmental biology, axon, Centrosome, Neurons, 0303 health sciences, General Immunology and Microbiology, Biochemistry, Genetics and Molecular Biology(all), General Neuroscience, Articles, Axons, Cell biology, hiPSC‐derived neuron, medicine.anatomical_structure, nervous system, Cell Adhesion, Polarity & Cytoskeleton, Stem cell, 030217 neurology & neurosurgery, Function (biology), Genetics and Molecular Biology(all), Neuroscience |
| الوصف: | Axon formation critically relies on local microtubule remodeling and marks the first step in establishing neuronal polarity. However, the function of the microtubule‐organizing centrosomes during the onset of axon formation is still under debate. Here, we demonstrate that centrosomes play an essential role in controlling axon formation in human‐induced pluripotent stem cell (iPSC)‐derived neurons. Depleting centrioles, the core components of centrosomes, in unpolarized human neuronal stem cells results in various axon developmental defects at later stages, including immature action potential firing, mislocalization of axonal microtubule‐associated Trim46 proteins, suppressed expression of growth cone proteins, and affected growth cone morphologies. Live‐cell imaging of microtubules reveals that centriole loss impairs axonal microtubule reorganization toward the unique parallel plus‐end out microtubule bundles during early development. We propose that centrosomes mediate microtubule remodeling during early axon development in human iPSC‐derived neurons, thereby laying the foundation for further axon development and function. Live‐cell imaging of centriole‐depleted cultured neurons demonstrates the essential role of human centrosomes in regulating various aspects of axon maturation and function via microtubule network reorganization. |
| وصف الملف: | application/pdf |
| تدمد: | 1460-2075 0261-4189 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::18e265545539f5ff24ffdaf24ff93a97Test https://doi.org/10.15252/embj.2020106798Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....18e265545539f5ff24ffdaf24ff93a97 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602075 02614189 |
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