Role of the Adherens Junction Protein Fascin in the Regulation of Tight Junction Permeability in the Mouse Mammary Gland
Abstract
An adenovirus-based gene delivery to the mouse mammary gland and cultured cells was developed. This system was used to express a truncation mutant of the tight junction protein occludin. Occludin and the tight junction complex proteins ZO 1 and claudin-1 left the tight junction following transgene expression, demonstrating tight junction disruption. Truncated occludin expression caused apoptosis in the mouse mammary gland epithelium and in cultured cells. The apoptotic mediator caspase-8 was activated within 24 hours of viral transduction. The caspase-8 downstream target caspase-3 was proteolytically activated and beta-catenin, one of many caspase-3 downstream targets, was cleaved within 24 hours of viral transduction. Caspase-8 is the chief regulatory caspase of the death inducing signaling complex (DISC) pathway. Early activation of caspase-8 suggests DISC mediation of the observed apoptosis. PTEN is a regulatory lipid phosphatase whose activity has been shown to attenuate Akt activity, correlating with DISC activation. PTEN localizes to the tight junction of epithelial cell monolayers. This has led to our current hypothesis: "PTEN is released from the tight junction and redistributes to lipid rafts containing DISC precursors. PTEN attenuates Akt activity in these rafts allowing DISC activation."
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA436567
Entities
People
- Margaret Neville
- Neal E. Beeman
Organizations
- University of Colorado Health