MICALs是一类保守的黄素蛋白氧化还原酶家族，在丛状蛋白介导的轴突排斥中发挥作用。

MICALs, a family of conserved flavoprotein oxidoreductases, function in plexin-mediated axonal repulsion.

作者信息

Terman Jonathan R, Mao Tianyi, Pasterkamp R Jeroen, Yu Hung-Hsiang, Kolodkin Alex L

机构信息

Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.

出版信息

Cell. 2002 Jun 28;109(7):887-900. doi: 10.1016/s0092-8674(02)00794-8.

DOI:10.1016/s0092-8674(02)00794-8

PMID:12110185

Abstract

Members of the semaphorin family of secreted and transmembrane proteins utilize plexins as neuronal receptors to signal repulsive axon guidance. It remains unknown how plexin proteins are directly linked to the regulation of cytoskeletal dynamics. Here, we show that Drosophila MICAL, a large, multidomain, cytosolic protein expressed in axons, interacts with the neuronal plexin A (PlexA) receptor and is required for Semaphorin 1a (Sema-1a)-PlexA-mediated repulsive axon guidance. In addition to containing several domains known to interact with cytoskeletal components, MICAL has a flavoprotein monooxygenase domain, the integrity of which is required for Sema-1a-PlexA repulsive axon guidance. Vertebrate orthologs of Drosophila MICAL are neuronally expressed and also interact with vertebrate plexins, and monooxygenase inhibitors abrogate semaphorin-mediated axonal repulsion. These results suggest a novel role for oxidoreductases in repulsive neuronal guidance.

摘要

分泌型和跨膜型信号素家族的成员利用丛状蛋白作为神经元受体来发出轴突导向排斥信号。目前尚不清楚丛状蛋白如何直接与细胞骨架动力学的调节相关联。在此，我们表明果蝇MICAL，一种在轴突中表达的大型多结构域胞质蛋白，与神经元丛状蛋白A（PlexA）受体相互作用，并且是信号素1a（Sema-1a）-PlexA介导的排斥性轴突导向所必需的。除了含有几个已知与细胞骨架成分相互作用的结构域外，MICAL还有一个黄素蛋白单加氧酶结构域，其完整性是Sema-1a-PlexA排斥性轴突导向所必需的。果蝇MICAL的脊椎动物直系同源物在神经元中表达，并且也与脊椎动物丛状蛋白相互作用，单加氧酶抑制剂可消除信号素介导的轴突排斥。这些结果表明氧化还原酶在排斥性神经元导向中具有新作用。