Hirai Yohei, Nelson Celeste M, Yamazaki Kyoko, Takebe Kyoko, Przybylo Jennifer, Madden Benjamin, Radisky Derek C
Department of Morphoregulation, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
J Cell Sci. 2007 Jun 15;120(Pt 12):2032-43. doi: 10.1242/jcs.006247. Epub 2007 May 29.
Epimorphin (also known as syntaxin 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 alphav-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.
表皮形态发生素（也称为 syntaxin 2）由乳腺、肺、肝、结肠、胰腺和其他组织的基质细胞分泌时，作为一种上皮形态发生原发挥作用，但同一分子在细胞内发挥作用以介导膜融合。这种缺乏信号序列且在 C 末端含有跨膜结构域的分子如何穿过质膜并分泌成为形态发生原，以及它如何启动形态发生事件尚不清楚。在这里，我们表明表皮形态发生素通过一种非经典机制分泌，类似于先前描述的无信号肽蛋白 FGF1 的分泌机制，并且我们确定了负责从细胞转运和分泌的关键分子元件。我们还表明，分泌的表皮形态发生素与靶上皮细胞上含αv整合素的受体结合，导致特定下游信号通路的激活并诱导上皮形态发生。这些发现为表皮形态发生素如何作为上皮形态发生原发挥作用提供了关键见解。
