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: [email protected].
  • 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: [email protected].
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.