Interaction of Axonal Chondrolectin with Collagen XIXa1 Is Necessary for Precise Neuromuscular Junction Formation

被引：14

作者：

Oprisoreanu, Ana-Maria ^{[1
]}

Smith, Hannah L. ^{[1
]}

Arya, Sukrat ^{[3
]}

Webster, Richard ^{[3
]}

Zhong, Zhen ^{[1
,4
]}

Wehner, Daniel ^{[1
,5
]}

Cardozo, Marcos J. ^{[1
]}

Becker, Thomas ^{[1
,2
]}

Talbot, Kevin ^{[3
]}

Becker, Catherina G. ^{[1
,2
]}

机构：

[1] Univ Edinburgh, Ctr Discovery Brain Sci, Chancellors Bldg,49 Little France Crescent, Edinburgh EH16 4SB, Midlothian, Scotland

[2] Univ Edinburgh, Euan MacDonald Ctr Motor Neurone Dis Res, Edinburgh, Midlothian, Scotland

[3] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, West Wing, Oxford OX3 9DU, England

[4] Zhejiang Univ, Sch Med, Ctr Neurosci, Hangzhou 310058, Zhejiang, Peoples R China

[5] Max Planck Inst Sci Light, Staudtstr 2, D-91058 Erlangen, Germany

来源：

CELL REPORTS | 2019年 / 29卷 / 05期

基金：

英国医学研究理事会;

关键词：

IN-VIVO; IDENTIFIED MOTONEURONS; MOUSE MODEL; GROWTH CONES; MOTOR; OUTGROWTH; SYNAPTOGENESIS; SURVIVAL; SMN; PROTEIN;

D O I：

10.1016/j.celrep.2019.09.033

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chondrolectin (Chodl) is needed for motor axon extension in zebrafish and is dysregulated in mouse models of spinal muscular atrophy (SMA). However, the mechanistic basis of Chodl function is not known. Here, we use Chodl-deficient zebrafish and mouse mutants to show that the absence of Chodl leads to anatomical and functional defects of the neuromuscular synapse. In zebrafish, the growth of an identified motor axon beyond an "en passant'' synapse and later axon branching from synaptic points are impaired, leading to functional deficits. Mechanistically, motor-neuron-autonomous Chodl function depends on its intracellular domain and on binding muscle-derived collagen XIXa1 by its extracellular C-type lectin domain. Our data support evolutionarily conserved roles of Chodl in synaptogenesis and provide evidence for a "synapse-first'' scenario of motor axon growth in zebrafish.

引用

页码：1082 / +

页数：27

共 70 条

[41] Early Functional Impairment of Sensory-Motor Connectivity in a Mouse Model of Spinal Muscular Atrophy [J].