肌肉 LIM 蛋白在损伤的成年中枢神经系统中表达，并促进轴突再生。

Muscle LIM Protein Is Expressed in the Injured Adult CNS and Promotes Axon Regeneration.

机构信息

Division of Experimental Neurology, Medical Faculty, Heinrich Heine University, Merowingerplatz 1a, 40225 Düsseldorf, Germany.

Department of Cell Physiology, Ruhr University of Bochum, Universitätsstraße 150, 44780 Bochum, Germany; Division of Experimental Neurology, Medical Faculty, Heinrich Heine University, Merowingerplatz 1a, 40225 Düsseldorf, Germany.

出版信息

Cell Rep. 2019 Jan 22;26(4):1021-1032.e6. doi: 10.1016/j.celrep.2018.12.026.

DOI:10.1016/j.celrep.2018.12.026

PMID:30673598

Abstract

Muscle LIM protein (MLP) has long been regarded as a muscle-specific protein. Here, we report that MLP expression is induced in adult rat retinal ganglion cells (RGCs) upon axotomy, and its expression is correlated with their ability to regenerate injured axons. Specific knockdown of MLP in RGCs compromises axon regeneration, while overexpression in vivo facilitates optic nerve regeneration and regrowth of sensory neurons without affecting neuronal survival. MLP accumulates in the cell body, the nucleus, and in axonal growth cones, which are significantly enlarged by its overexpression. Only the MLP fraction in growth cones is relevant for promoting axon extension. Additional data suggest that MLP acts as an actin cross-linker, thereby facilitating filopodia formation and increasing growth cone motility. Thus, MLP-mediated effects on actin could become a therapeutic strategy for promoting nerve repair.

摘要

肌肉 LIM 蛋白（MLP）长期以来一直被认为是一种肌肉特异性蛋白。在这里，我们报告说，MLP 在成年大鼠视网膜神经节细胞（RGC）轴突切断后被诱导表达，其表达与其再生损伤轴突的能力相关。在 RGC 中特异性敲低 MLP 会损害轴突再生，而体内过表达则促进视神经再生和感觉神经元的重新生长，而不影响神经元存活。MLP 在细胞体、核内以及轴突生长锥中积累，而过表达会显著增大生长锥。只有生长锥中的 MLP 部分与促进轴突延伸有关。其他数据表明，MLP 作为肌动蛋白交联剂起作用，从而促进丝状伪足的形成并增加生长锥的运动性。因此，MLP 对肌动蛋白的作用可能成为促进神经修复的治疗策略。