Bidirectional actin transport is influenced by microtubule and actin stability

Cell Mol Life Sci. 2015 Nov;72(21):4205-20. doi: 10.1007/s00018-015-1933-z. Epub 2015 Jun 5.

Abstract

Local and long-distance transport of cytoskeletal proteins is vital to neuronal maintenance and growth. Though recent progress has provided insight into the movement of microtubules and neurofilaments, mechanisms underlying the movement of actin remain elusive, in large part due to rapid transitions between its filament states and its diverse cellular localization and function. In this work, we integrated live imaging of rat sensory neurons, image processing, multiple regression analysis, and mathematical modeling to perform the first quantitative, high-resolution investigation of GFP-actin identity and movement in individual axons. Our data revealed that filamentous actin densities arise along the length of the axon and move short but significant distances bidirectionally, with a net anterograde bias. We directly tested the role of actin and microtubules in this movement. We also confirmed a role for actin densities in extension of axonal filopodia, and demonstrated intermittent correlation of actin and mitochondrial movement. Our results support a novel mechanism underlying slow component axonal transport, in which the stability of both microtubule and actin cytoskeletal components influence the mobility of filamentous actin.

Keywords: Actin; Axonal transport; Cytoskeleton; Microtubule; Slow component B.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Axonal Transport / physiology
  • Cells, Cultured
  • Cytoskeleton / metabolism
  • Depsipeptides / pharmacology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Mitochondria / metabolism
  • Models, Theoretical
  • Neurons / cytology
  • Neurons / metabolism
  • Nocodazole / pharmacology
  • Protein Transport
  • Pseudopodia / metabolism
  • Rats
  • Regression Analysis

Substances

  • Actins
  • Depsipeptides
  • jasplakinolide
  • Green Fluorescent Proteins
  • Nocodazole