title: Not just scaffolding: plectin regulates actin dynamics in cultured cells.
abstract: Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, we found that their actin cytoskeleton, including focal adhesion contacts, was developed more extensively than in wild-type cells. Also it failed to show characteristic short-term rearrangments in response to extracellular stimuli activating the Rho/Rac/Cdc42 signaling cascades. As a consequence, cell motility, adherence, and shear stress resistance were altered, and morphogenic processes were delayed. Furthermore, we show that plectin interacts with G-actin in vitro in a phosphatidylinositol-4,5-biphosphate-dependent manner and associates with actin stress fibers in living cells. The actin stress fiber phenotype of plectin-deficient fibroblasts could be reversed to a large degree by transient transfection of full-length plectin or plectin fragments containing the amino-terminal actin-binding domain (ABD). These results reveal a novel role of plectin as regulator of cellular processes involving actin filament dynamics that goes beyond its proposed role in scaffolding and mechanical stabilization of cells.
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, Vienna Biocenter, 1030 Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Andrä
authors.forename: B
authors.initials: B
authors.lastname: Nikolic
authors.forename: M
authors.initials: M
authors.lastname: Stöcher
authors.forename: D
authors.initials: D
authors.lastname: Drenckhahn
authors.forename: G
authors.initials: G
authors.lastname: Wiche
mesh_terms: D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D005656:Fungal Proteins / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D007381:Intermediate Filament Proteins / Q000502:physiology*; D051379:Mice; D010446:Peptide Fragments / Q000502:physiology; D051190:Plectin; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins; D012867:Skin; D014157:Transcription Factors / Q000502:physiology; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D007381:Intermediate Filament Proteins; C100530:PIP2 protein, S cerevisiae; D010446:Peptide Fragments; C495333:Plec protein, mouse; C495334:Plec protein, rat; D051190:Plectin; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins