Wdr47 Controls Neuronal Polarization through the Camsap Family Microtubule Minus-End-Binding Proteins

• Main Authors: Yawen Chen, Jianqun Zheng, Xiaowei Li, Lei Zhu, Zhifeng Shao, Xiumin Yan, Xueliang Zhu
• Format: Article
• Language: English
• Published: Elsevier 2020-04-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124720304265

Summary: Neurons require proper polarization for precise positioning and axon-dendrite formation. Their intrinsic regulators and underlying mechanisms are poorly understood. Here, we show that Wdr47 is a key polarization regulator. Wdr47-deficient newborn mice die of suffocation due to central nervous system defects including axonal tracts agenesis and slowed radial migration. Wdr47 deficiency represses the multipolar-bipolar transition of cortical neurons, reduces neurite tip-directed microtubule dynamics, and causes multi-axon formation. Overexpression of Wdr47 in wild-type neurons inhibits axon specification and neutralizes Taxol-induced neurite overgrowth and axon overproduction. Wdr47 interacts with the Camsap family of microtubule minus-end-binding proteins; associates with microtubules through Camsap3, whose gene disruption also causes multi-axons; and promotes Camsap3 accumulation in neurites of unpolarized neurons. Furthermore, Camsap overexpression rescues the polarization defects of Wdr47-deficient neurons. Our results indicate that Wdr47 facilitates proper neurite remodeling through Camsaps to fine-tune regional microtubule dynamics and organization during early stages of neuronal polarization. : Proper axon-dendrite polarity ensures unidirectional information processing of neurons. Here, Chen et al. uncover that Wdr47 is critical for neuronal intrinsic polarity control machinery. It functions through Camsap proteins to fine-tune regional microtubule dynamics and organization in unpolarized neurons. Wdr47-deficient neonatal mice die of developmental central nervous system defects. Keywords: Wdr47, Camsap, microtubule dynamics, multi-axon formation, multipolar-bipolar transition, neonatal death, radial migration