Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development

Neuron. 2014 Jun 4;82(5):1058-73. doi: 10.1016/j.neuron.2014.04.019.

Kah Wai Yau ¹, Sam F B van Beuningen ², Inês Cunha-Ferreira ², Bas M C Cloin ², Eljo Y van Battum ³, Lena Will ², Philipp Schätzle ², Roderick P Tas ², Jaap van Krugten ², Eugene A Katrukha ², Kai Jiang ², Phebe S Wulf ², Marina Mikhaylova ², Martin Harterink ², R Jeroen Pasterkamp ³, Anna Akhmanova ², Lukas C Kapitein ⁴, Casper C Hoogenraad ⁵

Affiliations

1 Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands; Department of Neuroscience, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands.
2 Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
3 Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands.
4 Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands. Electronic address: l.kapitein@uu.nl.
5 Cell Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands; Department of Neuroscience, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands. Electronic address: c.hoogenraad@uu.nl.

PMID: 24908486 DOI: 10.1016/j.neuron.2014.04.019

Abstract

In neurons, most microtubules are not associated with a central microtubule-organizing center (MTOC), and therefore, both the minus and plus-ends of these non-centrosomal microtubules are found throughout the cell. Microtubule plus-ends are well established as dynamic regulatory sites in numerous processes, but the role of microtubule minus-ends has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and laser-based microsurgery techniques, we show that the CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes to non-centrosomal microtubule minus-ends and is required for proper microtubule organization in neurons. CAMSAP2 stabilizes non-centrosomal microtubules and is required for neuronal polarity, axon specification, and dendritic branch formation in vitro and in vivo. Furthermore, we found that non-centrosomal microtubules in dendrites are largely generated by γ-Tubulin-dependent nucleation. We propose a two-step model in which γ-Tubulin initiates the formation of non-centrosomal microtubules and CAMSAP2 stabilizes the free microtubule minus-ends in order to control neuronal polarity and development.

Name
Email *

	Sorry, but the email address you supplied was invalid.