Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration

Selma Osmanagic-Myers, Martin Gregor, Gernot Walko, Gerald Burgstaller, Siegfried Reipert, Gerhard Wiche

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Plectin is a major intermediate filament (IF)-based cytolinker protein that stabilizes cells and tissues mechanically, regulates actin filament dynamics, and serves as a scaffolding platform for signaling molecules. In this study, we show that plectin deficiency is a cause of aberrant keratin cytoskeleton organization caused by a lack of orthogonal IF cross-linking. Keratin networks in plectin-deficient cells were more susceptible to osmotic shock-induced retraction from peripheral areas, and their okadaic acid-induced disruption (paralleled by stress-activated MAP kinase p38 activation) proceeded faster. Basal activities of the MAP kinase Erk1/2 and of the membrane-associated upstream protein kinases c-Src and PKCdelta were significantly elevated, and increased migration rates, as assessed by in vitro wound-closure assays and time-lapse microscopy, were observed. Forced expression of RACK1, which is the plectin-binding receptor protein for activated PKCdelta, in wild-type keratinocytes elevated their migration potential close to that of plectin-null cells. These data establish a link between cytolinker-controlled cytoarchitecture/scaffolding functions of keratin IFs and specific MAP kinase cascades mediating distinct cellular responses.

Original languageEnglish
Pages (from-to)557-568
Number of pages12
JournalThe Journal of Cell Biology (JCB)
Volume174
Issue number4
DOIs
Publication statusPublished - 14 Aug 2006

Keywords

  • Animals
  • Cell Movement/physiology
  • Cytoskeleton/metabolism
  • Enzyme Inhibitors/pharmacology
  • Intermediate Filament Proteins/metabolism
  • Keratinocytes/metabolism
  • Keratins/metabolism
  • MAP Kinase Signaling System/physiology
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Mitogen-Activated Protein Kinase 3/drug effects
  • Neuropeptides/drug effects
  • Okadaic Acid/pharmacology
  • Osmotic Pressure
  • Plakins/genetics
  • Plectin/genetics
  • Protein Kinase C-delta/drug effects
  • Receptors for Activated C Kinase
  • Stress, Physiological/metabolism
  • p38 Mitogen-Activated Protein Kinases/drug effects
  • src-Family Kinases/drug effects

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