LIM kinase 1 and cofilin regulate actin filament population required for dynamin-dependent apical carrier fission from the trans-Golgi network

Mol Biol Cell. 2009 Jan;20(1):438-51. doi: 10.1091/mbc.e08-08-0891. Epub 2008 Nov 5.

Abstract

The functions of the actin cytoskeleton in post-Golgi trafficking are still poorly understood. Here, we report the role of LIM Kinase 1 (LIMK1) and its substrate cofilin in the trafficking of apical and basolateral proteins in Madin-Darby canine kidney cells. Our data indicate that LIMK1 and cofilin organize a specialized population of actin filaments at the Golgi complex that is selectively required for the emergence of an apical cargo route to the plasma membrane (PM). Quantitative pulse-chase live imaging experiments showed that overexpression of kinase-dead LIMK1 (LIMK1-KD), or of LIMK1 small interfering RNA, or of an activated cofilin mutant (cofilin S3A), selectively slowed down the exit from the trans-Golgi network (TGN) of the apical PM marker p75-green fluorescent protein (GFP) but did not interfere with the apical PM marker glycosyl phosphatidylinositol-YFP or the basolateral PM marker neural cell adhesion molecule-GFP. High-resolution live imaging experiments of carrier formation and release by the TGN and analysis of peri-Golgi actin dynamics using photoactivatable GFP suggest a scenario in which TGN-localized LIMK1-cofilin regulate a population of actin filaments required for dynamin-syndapin-cortactin-dependent generation and/or fission of precursors to p75 transporters.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors / genetics
  • Actin Depolymerizing Factors / metabolism*
  • Actins / metabolism
  • Animals
  • Biomarkers / metabolism
  • Cell Line
  • Cell Polarity
  • Cytoskeleton / metabolism
  • Dogs
  • Dynamins / genetics
  • Dynamins / metabolism*
  • Golgi Apparatus / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lim Kinases / genetics
  • Lim Kinases / metabolism*
  • Models, Biological
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / metabolism
  • Protein Transport / physiology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptor, Nerve Growth Factor / genetics
  • Receptor, Nerve Growth Factor / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • trans-Golgi Network / metabolism*

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Biomarkers
  • Isoenzymes
  • Neural Cell Adhesion Molecules
  • RNA, Small Interfering
  • Receptor, Nerve Growth Factor
  • Recombinant Fusion Proteins
  • Lim Kinases
  • Dynamins