First Author | Chen Y | Year | 2020 |
Journal | Cell Rep | Volume | 31 |
Issue | 3 | Pages | 107526 |
PubMed ID | 32320668 | Mgi Jnum | J:298825 |
Mgi Id | MGI:6488816 | Doi | 10.1016/j.celrep.2020.107526 |
Citation | Chen Y, et al. (2020) Wdr47 Controls Neuronal Polarization through the Camsap Family Microtubule Minus-End-Binding Proteins. Cell Rep 31(3):107526 |
abstractText | 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. |