Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development.
Authors:
Yau, Kah Wai van Beuningen, Sam F B Cunha-Ferreira, Inês Cloin, Bas M C van Battum, Eljo Y Will, Lena Schätzle, Philipp Tas, Roderick P van Krugten, Jaap Katrukha, Eugene A Jiang, Kai Wulf, Phebe S Mikhaylova, Marina Harterink, Martin Pasterkamp, R Jeroen Akhmanova, Anna Kapitein, Lukas C Hoogenraad, Casper C
Citation:
Yau KW, etal., Neuron. 2014 Jun 4;82(5):1058-73. doi: 10.1016/j.neuron.2014.04.019.
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.