Journal article
The β-actin mRNA zipcode regulates epithelial adherens junction assembly but not maintenance
RNA (Cambridge), v 20(5), pp 689-701
01 May 2014
PMID: 24681968
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
This paper examines requirements for cytoskeletal remodeling during epithelial cell-cell contact. Antisense oligonucleotides that inhibit β-actin mRNA zipcode/ZBP1 interactions cause defects in adherens junction assembly.
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.
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Details
- Title
- The β-actin mRNA zipcode regulates epithelial adherens junction assembly but not maintenance
- Creators
- Natasha Gutierrez - Rutgers, The State University of New JerseyItua Eromobor - Rutgers, The State University of New JerseyRyan J. Petrie - National Institute of Dental and Craniofacial ResearchPavan Vedula - Rutgers, The State University of New JerseyLissette Cruz - Rutgers, The State University of New JerseyAlexis J. Rodriguez - Rutgers, The State University of New Jersey
- Publication Details
- RNA (Cambridge), v 20(5), pp 689-701
- Publisher
- Cold Spring Harbor Laboratory Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000334677800010
- Scopus ID
- 2-s2.0-84898969383
- Other Identifier
- 991020100087504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology