title: The β-actin mRNA zipcode regulates epithelial adherens junction assembly but not maintenance.
abstract: Epithelial cell-cell contact stimulates actin cytoskeleton remodeling to down-regulate branched filament polymerization-driven lamellar protrusion and subsequently to assemble linear actin filaments required for E-cadherin anchoring during adherens junction complex assembly. In this manuscript, we demonstrate that de novo protein synthesis, the β-actin 3' UTR, and the β-actin mRNA zipcode are required for epithelial adherens junction complex assembly but not maintenance. Specifically, we demonstrate that perturbing cell-cell contact-localized β-actin monomer synthesis causes epithelial adherens junction assembly defects. Consequently, inhibiting β-actin mRNA zipcode/ZBP1 interactions with β-actin mRNA zipcode antisense oligonucleotides, to intentionally delocalize β-actin monomer synthesis, is sufficient to perturb adherens junction assembly following epithelial cell-cell contact. Additionally, we demonstrate active RhoA, the signal required to drive zipcode-mediated β-actin mRNA targeting, is localized at epithelial cell-cell contact sites in a β-actin mRNA zipcode-dependent manner. Moreover, chemically inhibiting Src kinase activity prevents the local stimulation of β-actin monomer synthesis at cell-cell contact sites while inhibiting epithelial adherens junction assembly. Together, these data demonstrate that epithelial cell-cell contact stimulates β-actin mRNA zipcode-mediated monomer synthesis to spatially regulate actin filament remodeling, thereby controlling adherens junction assembly to modulate cell and tissue adhesion.
authors.forename: Natasha
authors.initials: N
authors.lastname: Gutierrez
authors.forename: Itua
authors.initials: I
authors.lastname: Eromobor
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Petrie
authors.forename: Pavan
authors.initials: P
authors.lastname: Vedula
authors.forename: Lissette
authors.initials: L
authors.lastname: Cruz
authors.forename: Alexis J
authors.initials: AJ
authors.lastname: Rodriguez
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics; D000199:Actins / Q000235:genetics* / Q000378:metabolism; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C485731:ZBP1 protein, human; D020742:rhoA GTP-Binding Protein
keywords: RhoA and Src signaling; actin cytoskeleton regulation; actin mRNA zipcodes; adherens junction assembly; translation regulation