Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity

• Published in: eLife Vol. 9
• Main Authors: He, Liu, Kooistra, Robbelien, Das, Ravi, Oudejans, Ellen, van Leen, Eric, Ziegler, Johannes, Portegies, Sybren, de Haan, Bart, van Regteren Altena, Anna, Stucchi, Riccardo, Altelaar, Af Maarten, Wieser, Stefan, Krieg, Michael, Hoogenraad, Casper C, Harterink, Martin
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 15.04.2020; eLife Sciences Publications, Ltd
• Subjects: Animals; Ankyrin; Ankyrins; Ankyrins - physiology; Axonal transport; Axons; Caenorhabditis elegans; Caenorhabditis elegans Proteins - physiology; Cell Biology; Cell Polarity - physiology; Cells, Cultured; Cerebral Cortex - physiology; CRMP; Cytoskeleton; Cytoskeleton - physiology; Defects; Dendrites; Kinesin; Localization; Locomotion; microtubule; Microtubules - physiology; Nerve Growth Factors - physiology; Nerve Tissue Proteins; Nervous system; neuron polarity; Neurons; Neurons - physiology; Neuroscience; Polarity; Protein transport; Proteins; Statistical analysis; Young adults; microtubule; C. elegans; cell biology; kinesin; neuroscience; neuron polarity; Ankyrin; CRMP
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.55111

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 , 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.