Axon morphogenesis and maintenance require an evolutionary conserved safeguard function of Wnk kinases antagonizing Sarm and Axed

被引：22

作者：

Izadifar, Azadeh ^{[1
,2
,3
]}

Courchet, Julien ^{[4
,5
]}

Virga, Daniel M. ^{[5
]}

Verreet, Tine ^{[2
,3
]}

Hamilton, Stevie ^{[5
]}

Ayaz, Derya ^{[2
,3
]}

Misbaer, Anke ^{[2
,3
]}

Vandenbogaerde, Sofie ^{[2
,3
]}

Monteiro, Laloe ^{[4
]}

Petrovic, Milan ^{[2
,3
]}

Sachse, Sonja ^{[2
,3
]}

Yan, Bing ^{[2
,3
]}

Erfurth, Maria-Luise ^{[2
,3
]}

Dascenco, Dan ^{[2
,3
]}

Kise, Yoshiaki ^{[7
]}

Yan, Jiekun ^{[2
,3
]}

Edwards-Faret, Gabriela ^{[1
,2
,3
]}

Lewis, Tommy ^{[5
,8
]}

Polleux, Franck ^{[5
,6
]}

Schmucker, Dietmar ^{[1
,2
,3
]}

机构：

[1] Life & Med Sci Inst LIMES, Bonn, Germany

[2] VIB Ctr Brain & Dis Res, Leuven, Belgium

[3] Katholieke Univ Leuven, Dept Neurosci, Leuven, Belgium

[4] Univ Lyon, Univ Claude Bernard Lyon 1, Inst NeuroMyoGene, CNRS UMR 5310,INSERM U1217, F-69622 Villeurbanne, France

[5] Columbia Univ, Mortimer B Zuckerman Mind Brain Behav Inst, Dept Neurosci, New York, NY 10027 USA

[6] Columbia Univ, Kavli Inst Brain Sci, New York, NY 10027 USA

[7] Univ Tokyo, Tokyo, Japan

[8] Oklahoma Med Res Fdn, Aging & Metab Program, 825 NE 13th St, Oklahoma City, OK 73104 USA

来源：

NEURON | 2021年 / 109卷 / 18期

关键词：

NEUROPATHY TYPE-II; AUTONOMIC NEUROPATHY; WALLERIAN DEGENERATION; PROTEIN-KINASES; INJURY; DROSOPHILA; MUTATIONS; DEATH; SPAK; ACTIVATION;

D O I：

10.1016/j.neuron.2021.07.006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The molecular and cellular mechanisms underlying complex axon morphogenesis are still poorly understood. We report a novel, evolutionary conserved function for the Drosophila Wnk kinase (dWnk) and its mammalian orthologs, WNK1 and 2, in axon branching. We uncover that dWnk, together with the neuroprotective factor Nmnat, antagonizes the axon-destabilizing factors D-Sarm and Axundead (Axed) during axon branch growth, revealing a developmental function for these proteins. Overexpression of D-Sarm or Axed results in axon branching defects, which can be blocked by overexpression of dWnk or Nmnat. Surprisingly, Wnk kinases are also required for axon maintenance of adult Drosophila and mouse cortical pyramidal neurons. Requirement of Wnk for axon maintenance is independent of its developmental function. Inactivation of dWnk or mouse Wnk1/2 in mature neurons leads to axon degeneration in the adult brain. Therefore, Wnk kinases are novel signaling components that provide a safeguard function in both developing and adult axons.

引用

页码：2864 / +

页数：29