LIM and SH3 protein 1 localizes to the leading edge of protruding lamellipodia and regulates axon development

Mol Biol Cell. 2020 Nov 15;31(24):2718-2732. doi: 10.1091/mbc.E20-06-0366. Epub 2020 Sep 30.


The actin cytoskeleton drives cell motility and is essential for neuronal development and function. LIM and SH3 protein 1 (LASP1) is a unique actin-binding protein that is expressed in a wide range of cells including neurons, but its roles in cellular motility and neuronal development are not well understood. We report that LASP1 is expressed in rat hippocampus early in development, and this expression is maintained through adulthood. High-resolution imaging reveals that LASP1 is selectively concentrated at the leading edge of lamellipodia in migrating cells and axonal growth cones. This local enrichment of LASP1 is dynamically associated with the protrusive activity of lamellipodia, depends on the barbed ends of actin filaments, and requires both the LIM domain and the nebulin repeats of LASP1. Knockdown of LASP1 in cultured rat hippocampal neurons results in a substantial reduction in axonal outgrowth and arborization. Finally, loss of the Drosophila homologue Lasp from a subset of commissural neurons in the developing ventral nerve cord produces defasciculated axon bundles that do not reach their targets. Together, our data support a novel role for LASP1 in actin-based lamellipodial protrusion and establish LASP1 as a positive regulator of both in vitro and in vivo axon development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Animals
  • Axons / metabolism*
  • Cell Movement / physiology
  • Cytoskeletal Proteins / metabolism
  • Female
  • LIM Domain Proteins / metabolism
  • LIM Domain Proteins / physiology
  • Male
  • Microfilament Proteins / metabolism*
  • Microfilament Proteins / physiology
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Neurogenesis / physiology
  • Neurons / metabolism
  • Primary Cell Culture
  • Pseudopodia / metabolism*
  • Pseudopodia / physiology
  • Rats


  • Actins
  • Cytoskeletal Proteins
  • LIM Domain Proteins
  • Lasp1 protein, rat
  • Microfilament Proteins
  • Nerve Tissue Proteins