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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Movement / physiology
-
Cytoskeleton / metabolism*
-
Cytoskeleton / ultrastructure
-
Enzyme Inhibitors / pharmacology
-
Intermediate Filament Proteins / metabolism*
-
Keratinocytes / metabolism
-
Keratinocytes / ultrastructure
-
Keratins / metabolism*
-
MAP Kinase Signaling System / physiology*
-
Mice
-
Mice, Knockout
-
Microscopy, Electron, Transmission
-
Mitogen-Activated Protein Kinase 3 / drug effects
-
Mitogen-Activated Protein Kinase 3 / metabolism
-
Neuropeptides / drug effects
-
Neuropeptides / metabolism
-
Okadaic Acid / pharmacology
-
Osmotic Pressure
-
Plakins / genetics
-
Plakins / metabolism*
-
Plectin / genetics
-
Plectin / metabolism*
-
Protein Kinase C-delta / drug effects
-
Protein Kinase C-delta / metabolism
-
Receptors for Activated C Kinase
-
Stress, Physiological / metabolism
-
p38 Mitogen-Activated Protein Kinases / drug effects
-
p38 Mitogen-Activated Protein Kinases / metabolism
-
src-Family Kinases / drug effects
-
src-Family Kinases / metabolism
Substances
-
Enzyme Inhibitors
-
Intermediate Filament Proteins
-
Neuropeptides
-
Plakins
-
Plec protein, mouse
-
Plectin
-
RACK1 protein, mouse
-
Receptors for Activated C Kinase
-
Okadaic Acid
-
Keratins
-
src-Family Kinases
-
Protein Kinase C-delta
-
Mitogen-Activated Protein Kinase 3
-
p38 Mitogen-Activated Protein Kinases