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

作者：Ya‐Wen Chen, Jianqun Zheng, Xiaowei Li, Lei Zhu, Zhifeng Shao, Xiumin Yan, Xueliang Zhu · 发表于：Cell Reports · 年份：2020 · DOI：10.1016/j.celrep.2020.107526 · 被引用次数：33 · 研究领域：Microtubule and mitosis dynamics、Neurogenesis and neuroplasticity mechanisms、Neuroscience and Neuropharmacology Research

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.