title: Palladin regulates cell and extracellular matrix interaction through maintaining normal actin cytoskeleton architecture and stabilizing beta1-integrin.
abstract: Cell and extracellular matrix (ECM) interaction plays an important role in development and normal cellular function. Cell adhesion and cell spreading on ECM are two basic cellular behaviors related to cell-ECM interaction. Here we show that palladin, a novel actin cytoskeleton-associated protein, is actively involved in the regulation of cell-ECM interaction. It was found that palladin-deficient mouse embryonic fibroblasts (MEFs) display decreased cell adhesion and compromised cell spreading on various ECMs. Disorganized actin cytoskeleton architecture characterized by faint stress fibers, less lamellipodia and focal adhesions can account for the weakened cell-ECM interaction in palladin(-/-) MEFs. Furthermore, decreased polymerized filament actin and increased globular actin can be observed in palladin(-/-) MEFs, strongly suggesting that palladin is essential for the formation or stabilization of polymerized filament actin. Elevated phospho-cofilin level and proper responses in cofilin phosphorylation to either Rho signal agonist or antagonist in palladin(-/-) MEFs indicate that disrupted stress fibers in palladin(-/-) MEFs is not associated with cofilin phosphorylation. More interestingly, the protein level of ECM receptor beta1-integrin is dramatically decreased in MEFs lacking palladin. Down-regulation of beta1-integrin protein can be restored by proteasome inhibitor MG-132 treatment. All these data implicate that palladin is essential for cell-ECM interaction through maintaining normal actin cytoskeleton architecture and stabilizing beta1-integrin protein.
authors.affiliation: Laboratory of Genetic Engineering, Department of Medical Genetics, Institute of Health Sciences, Shanghai Jiao Tong University Medical School & Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, Shanghai 200025, PR China.
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Liu
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Luo
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.forename: Yue-E
authors.initials: YE
authors.lastname: Jin
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Ming-Min
authors.initials: MM
authors.lastname: Gu
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Lu
authors.forename: Zhu-Gang
authors.initials: ZG
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D002450:Cell Communication; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019012:Integrin beta1 / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; C495811:Cfl1 protein, mouse; D051338:Cofilin 1; D003598:Cytoskeletal Proteins; D019012:Integrin beta1; D010750:Phosphoproteins; D012333:RNA, Messenger; C485873:palladin protein, mouse; D020741:rho GTP-Binding Proteins