Cunha-Ferreira, Inês, Chazeau, Anaël, Buijs, Robin R, Stucchi, Riccardo, Will, Lena, Pan, Xingxiu, Adolfs, Youri, van der Meer, Christiaan, Wolthuis, Joanna C, Kahn, Olga I, Schätzle, Philipp, Altelaar, Maarten, Pasterkamp, R Jeroen, Kapitein, Lukas C, Hoogenraad, Casper C, Sub Cell Biology, Afd Biomol.Mass Spect. and Proteomics, Celbiologie, Biomolecular Mass Spectrometry and Proteomics, Sub Cell Biology, Afd Biomol.Mass Spect. and Proteomics, Celbiologie, and Biomolecular Mass Spectrometry and Proteomics
Summary Neuron morphology and function are highly dependent on proper organization of the cytoskeleton. In neurons, the centrosome is inactivated early in development, and acentrosomal microtubules are generated by mechanisms that are poorly understood. Here, we show that neuronal migration, development, and polarization depend on the multi-subunit protein HAUS/augmin complex, previously described to be required for mitotic spindle assembly in dividing cells. The HAUS complex is essential for neuronal microtubule organization by ensuring uniform microtubule polarity in axons and regulation of microtubule density in dendrites. Using live-cell imaging and high-resolution microscopy, we found that distinct HAUS clusters are distributed throughout neurons and colocalize with γ-TuRC, suggesting local microtubule nucleation events. We propose that the HAUS complex locally regulates microtubule nucleation events to control proper neuronal development., Graphical Abstract, Highlights • The HAUS/augmin complex regulates migration and polarization in vivo • Axonal and dendritic development are regulated by HAUS/augmin complex • HAUS/augmin regulates microtubule density in dendrites and polarity in axons • Discrete clusters of HAUS/augmin regulate local microtubule nucleation in neurons, Cunha-Ferreira et al. report that the HAUS/augmin complex regulates neuronal migration, polarization, and development. In neurons, the HAUS complex is distributed as discrete clusters regulating local microtubule nucleation. These findings shed light into how microtubules are generated in developing neurons after centrosome inactivation in early development.