Non-classical export of epimorphin and its adhesion to αv-integrin in regulation of epithelial morphogenesis

Yohei Hirai, Celeste M. Nelson, Kyoko Yamazaki, Kyoko Takebe, Jennifer Przybylo, Benjamin Madden, Derk C. Radisky

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Epimorphin (also known as synthaxin 2) acts as an epithelial morphogen when secreted by stromal cells of the mammary gland, lung, liver, colon, pancreas and other tissues, but the same molecule functions within the cell to mediate membrane fusion. How this molecule, which lacks a signal sequence and contains a transmembrane domain at the C-terminus, translocates across the plasma membrane and is secreted to become a morphogen, and how it initiates morphogenic events is not clear. Here, we show that epimorphin is secreted through a non-classical mechanism, similar to that previously described for secretion of the leaderless protein FGF1, and we identify the key molecular elements responsible for translocation and secretion from the cell. We also show that secreted epimorphin binds to αv-integrin-containing receptors on target epithelial cells, leading to activation of specific downstream signaling pathways and induction of epithelial morphogenesis. These findings provide key insight into how epimorphin functions as an epithelial morphogen.

Original languageEnglish (US)
Pages (from-to)2032-2043
Number of pages12
JournalJournal of cell science
Volume120
Issue number12
DOIs
StatePublished - Jun 15 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Keywords

  • Epimorphin
  • Integrin
  • Membrane translocation
  • Morphogenesis
  • t-SNARE

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