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

• Type of Material: Article
• Authors: Stephanie L Pollitt, Emory University; Kenneth Myers, Emory University; Jin Yoo, Emory University; James Zheng, Emory University
• Language: English
• Date: 2020-11-15
• Publisher: AMER SOC CELL BIOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Pollitt et al. “ASCB®
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1091/mbc.E20-06-0366
• Title of Journal or Parent Work: MOLECULAR BIOLOGY OF THE CELL
• Volume: 31
• Issue: 24
• Start Page: 2718
• End Page: 2732
• Grant/Funding Information: This research project was supported in part by research grants from the NHS to J.Q.Z. (GM083889), a Ruth L. Kirschstein National Research Service Award (NRSA) predoctoral fellowship to S.L.P. (NS101786), and a NRSA postdoctoral fellowship to K.R.M. (NS092342), as well as by the Emory University Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience National Institute of Neurological Disorders and Stroke Core Facilities grant (5P30NS055077).
• Keywords: BINDING-PROTEINS; MIGRATION; PROLIFERATION; HIPPOCAMPUS; Cell Biology; SYNAPSES; ACTIN DYNAMICS; GROWTH CONE MOTILITY; ARP2/3; CELL-ADHESION; LASP-1; Life Sciences & Biomedicine; Science & Technology
• Research Categories: Biology, Cell; Biology, Neuroscience

Abstract

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.