Regulation of microtubule-associated motors drives intermediate filament network polarization

J Cell Biol. 2017 Jun 5;216(6):1689-1703. doi: 10.1083/jcb.201607045. Epub 2017 Apr 21.

Abstract

Intermediate filaments (IFs) are key players in the control of cell morphology and structure as well as in active processes such as cell polarization, migration, and mechanoresponses. However, the regulatory mechanisms controlling IF dynamics and organization in motile cells are still poorly understood. In this study, we investigate the mechanisms leading to the polarized rearrangement of the IF network along the polarity axis. Using photobleaching and photoconversion experiments in glial cells expressing vimentin, glial fibrillary acidic protein, and nestin, we show that the distribution of cytoplasmic IFs results from a continuous turnover based on the cooperation of an actin-dependent retrograde flow and anterograde and retrograde microtubule-dependent transports. During wound-induced astrocyte polarization, IF transport becomes directionally biased from the cell center toward the cell front. Such asymmetry in the transport is mainly caused by a Cdc42- and atypical PKC-dependent inhibition of dynein-dependent retrograde transport. Our results show how polarity signaling can affect the dynamic turnover of the IF network to promote the polarization of the network itself.

Publication types

  • Video-Audio Media
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Polarity*
  • Dyneins / genetics
  • Dyneins / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Intermediate Filaments / metabolism*
  • Microscopy, Video
  • Microtubules / metabolism*
  • Nestin / metabolism
  • Neuroglia / metabolism*
  • Neuroglia / pathology
  • Optical Imaging
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • RNA Interference
  • Rats
  • Signal Transduction
  • Time Factors
  • Transfection
  • Vimentin / metabolism
  • Wound Healing
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism*

Substances

  • Actins
  • Glial Fibrillary Acidic Protein
  • NES protein, human
  • Nestin
  • Vimentin
  • PKC-3 protein
  • Protein Kinase C
  • Dyneins
  • cdc42 GTP-Binding Protein