Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity
The development of a polarized neuron relies on the selective transport of proteins to axons and dendrites. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is poorly understo...
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eLife Sciences Publications Ltd
2020-04-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/55111 |
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author | Liu He Robbelien Kooistra Ravi Das Ellen Oudejans Eric van Leen Johannes Ziegler Sybren Portegies Bart de Haan Anna van Regteren Altena Riccardo Stucchi AF Maarten Altelaar Stefan Wieser Michael Krieg Casper C Hoogenraad Martin Harterink |
author_facet | Liu He Robbelien Kooistra Ravi Das Ellen Oudejans Eric van Leen Johannes Ziegler Sybren Portegies Bart de Haan Anna van Regteren Altena Riccardo Stucchi AF Maarten Altelaar Stefan Wieser Michael Krieg Casper C Hoogenraad Martin Harterink |
author_sort | Liu He |
collection | DOAJ |
description | The development of a polarized neuron relies on the selective transport of proteins to axons and dendrites. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is poorly understood. Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubule-associated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals. |
first_indexed | 2024-12-10T05:03:35Z |
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id | doaj.art-0af7cedb8c114e9684ed3ed0d51fcc6d |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-12-10T05:03:35Z |
publishDate | 2020-04-01 |
publisher | eLife Sciences Publications Ltd |
record_format | Article |
series | eLife |
spelling | doaj.art-0af7cedb8c114e9684ed3ed0d51fcc6d2022-12-22T02:01:18ZengeLife Sciences Publications LtdeLife2050-084X2020-04-01910.7554/eLife.55111Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarityLiu He0Robbelien Kooistra1https://orcid.org/0000-0003-4576-8964Ravi Das2Ellen Oudejans3Eric van Leen4Johannes Ziegler5Sybren Portegies6Bart de Haan7Anna van Regteren Altena8Riccardo Stucchi9AF Maarten Altelaar10Stefan Wieser11Michael Krieg12Casper C Hoogenraad13Martin Harterink14https://orcid.org/0000-0002-8256-6651Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsNeurophotonics and Mechanical Systems Biology, ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, SpainCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsFast live-cell superresolution microscopy, ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, SpainCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsFast live-cell superresolution microscopy, ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, SpainNeurophotonics and Mechanical Systems Biology, ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, SpainCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands; Department of Neuroscience, Genentech, Inc, South San Francisco, United StatesCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsThe development of a polarized neuron relies on the selective transport of proteins to axons and dendrites. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is poorly understood. Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubule-associated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.https://elifesciences.org/articles/55111neuron polaritymicrotubulekinesinCRMPAnkyrin |
spellingShingle | Liu He Robbelien Kooistra Ravi Das Ellen Oudejans Eric van Leen Johannes Ziegler Sybren Portegies Bart de Haan Anna van Regteren Altena Riccardo Stucchi AF Maarten Altelaar Stefan Wieser Michael Krieg Casper C Hoogenraad Martin Harterink Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity eLife neuron polarity microtubule kinesin CRMP Ankyrin |
title | Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity |
title_full | Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity |
title_fullStr | Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity |
title_full_unstemmed | Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity |
title_short | Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity |
title_sort | cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity |
topic | neuron polarity microtubule kinesin CRMP Ankyrin |
url | https://elifesciences.org/articles/55111 |
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