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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Main Authors: 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
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-04-01
Series:eLife
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Online Access:https://elifesciences.org/articles/55111
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spelling doaj-0af7cedb8c114e9684ed3ed0d51fcc6d2021-05-05T21:00:01ZengeLife 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
collection DOAJ
language English
format Article
sources DOAJ
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
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
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
title 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_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_sort cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2020-04-01
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.
topic neuron polarity
microtubule
kinesin
CRMP
Ankyrin
url https://elifesciences.org/articles/55111
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