Saturation of, and competition for entry into, the apical secretory pathway

Alan D. Marmorstein, Karl G. Csaky, Judit Baffi, Linda Lam, Firas Rahaal, Enrique Rodriguez-Boulan

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

To investigate mechanisms of apical sorting in the secretory pathway of epithelial cells, we expressed varying amounts of the 165 amino acid isoform of vascular endothelial growth factor (VEGF165) and transforming growth factor β1 (TGF-β1) via replication defective adenoviruses. Apical sorting of both proteins was efficient at low expression levels but saturated or was reversed at high expression levels. High expression levels of TGF-β1 were effective at competing VEGF165 out of the apical pathway; however, VEGF165 did not compete out TGF-β1. Tunicamycin inhibition experiments showed that the apical polarity of VEGF165 was independent of N- glycosylation. We conclude that the apical sorting of these two molecules is a saturable, signal-mediated process, involving competition for apical sorting receptors. The sorting of the two proteins does not appear to involve N-glycans as sorting signals, or lectin sorters. The observations are particularly relevant to gene therapy because they demonstrate that overexpression of a transgene can result in undesirable missorting of the encoded protein.

Original languageEnglish (US)
Pages (from-to)3248-3253
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number7
DOIs
StatePublished - Mar 28 2000

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Saturation of, and competition for entry into, the apical secretory pathway'. Together they form a unique fingerprint.

  • Cite this