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

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.
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