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

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

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.

Keywords: CNS; PNS; actin; axon regeneration; cysteine rich protein 3; growth cone; muscle LIM protein; optic nerve; retinal ganglion cell; sensory neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axotomy
  • COS Cells
  • Central Nervous System / metabolism*
  • Central Nervous System / pathology
  • Chlorocebus aethiops
  • Gene Expression Regulation*
  • Growth Cones / metabolism*
  • LIM Domain Proteins / biosynthesis*
  • LIM Domain Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Muscle Proteins / biosynthesis*
  • Muscle Proteins / genetics
  • Nerve Regeneration*
  • Optic Nerve / physiology*
  • Rats
  • Retinal Ganglion Cells / metabolism*
  • Retinal Ganglion Cells / pathology
  • Vesicular Transport Proteins / biosynthesis*
  • Vesicular Transport Proteins / genetics

Substances

  • LIM Domain Proteins
  • Marcksl1 protein, rat
  • Muscle Proteins
  • Vesicular Transport Proteins
  • cysteine and glycine-rich protein 3