CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane.
CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane.
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CHL1 通过将 ERM 蛋白募集到质膜所需的基序促进 Sema3A 诱导的生长锥塌陷和神经突细化。
DOI：
10.1111/j.1471-4159.2007.05013.x
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发表时间：
2008
影响因子：
4.7
通讯作者：
Maness,PatriciaF
中科院分区：
文献类型：
--
作者：
Schlatter,MonikaC;Buhusi,Mona;Wright,AmandaG;Maness,PatriciaF
L1（CHL 1）的同源物是一种跨膜细胞粘附分子，在L1家族中的皮质神经元定位和树突投射中具有独特的发育功能，以及在促进整合素依赖性神经突生长和脑信号蛋白3A（Sema 3A）介导的轴突排斥中具有共同的功能。CHL 1介导这些不同功能的分子机制尚不清楚。在这里，使用细胞荧光测定证明CHL 1能够将埃兹蛋白（ezrin）（丝状肌动蛋白结合蛋白的埃兹蛋白-根蛋白-膜突蛋白（ERM）家族的成员）募集到质膜，并且这需要CHL 1胞质结构域中的近膜基序（RGGKYSV）。CHL 1中的这个序列被证明具有Sema 3A诱导的生长锥塌陷和皮层胚胎神经元中CHL 1依赖性神经突生长和分支所必需的新功能。此外，CHL 1对趋触细胞迁移和细胞粘附于纤连蛋白的刺激依赖于CHL 1/ERM募集基序。这些发现表明，CHL 1和ERM蛋白之间的直接或间接相互作用介导了Sema 3A诱导的生长锥塌陷以及神经突生长和分支，这是皮质发育中轴突导向和连接的重要决定因素。
Close homolog of L1 (CHL1) is a transmembrane cell adhesion molecule with unique developmental functions in cortical neuronal positioning and dendritic projection within the L1 family, as well as shared functions in promotion of integrin‐dependent neurite outgrowth and semaphorin3A (Sema3A)‐mediated axon repulsion. The molecular mechanisms by which CHL1 mediates these diverse functions are obscure. Here it is demonstrated using a cytofluorescence assay that CHL1 is able to recruit ezrin, a member of the ezrin‐radixin‐moesin (ERM) family of filamentous actin binding proteins to the plasma membrane, and that this requires a membrane‐proximal motif (RGGKYSV) in the CHL1 cytoplasmic domain. This sequence in CHL1 is shown to have novel functions necessary for Sema3A‐induced growth cone collapse and CHL1‐dependent neurite outgrowth and branching in cortical embryonic neurons. In addition, stimulation of haptotactic cell migration and cellular adhesion to fibronectin by CHL1 depends on the CHL1/ERM recruitment motif. These findings suggest that a direct or indirect interaction between CHL1 and ERM proteins mediates Sema3A‐induced growth cone collapse as well as neurite outgrowth and branching, which are essential determinants of axon guidance and connectivity in cortical development.