Hotchkiss Brain Institute, Department of Cell Biology and Anatomy, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada.
Dev Dyn. 2011 Dec;240(12):2657-72. doi: 10.1002/dvdy.22770.
In Xenopus laevis embryos, heparanase, the enzyme that degrades heparan sulfate, is synthesized as a preproheparanase (XHpaL) and processed to become enzymatically active (XHpa active). A short nonenzymatic heparanase splice variant (XHpaS) is also expressed. Using immunohistochemistry, Western blot, and heparanase promoter analysis, we studied the dynamic developmental expression of the three heparanases. Our results indicate that (1) all three isoforms are maternally expressed; (2) XHpaS is a developmental variant; (3) in the early embryo, heparanase is localized to both the plasma membrane and the nucleus; (4) several tissues express heparanase, but expression in the developing nervous system is most evident; (5) two promoters with distinct activities in different tissues drive heparanase expression; (6) Oct binding transcription factors may modulate heparanase promoter activity in the early embryo. These data argue that heparanase is expressed widely during development, but localization and levels are finely regulated.
在非洲爪蟾胚胎中,能够降解肝素硫酸的酶——肝素酶,最初被合成前体肝素酶(XHpaL),然后经加工成为有酶活性的(XHpa active)形式。同时,也有一个短的非酶切的肝素酶剪接变体(XHpaS)被表达。我们通过免疫组织化学、Western blot 和肝素酶启动子分析,研究了三种肝素酶的动态发育表达。结果表明:(1)所有三种同工酶都是母源性表达的;(2)XHpaS 是一种发育变体;(3)在早期胚胎中,肝素酶定位于质膜和核内;(4)有几个组织表达肝素酶,但在发育中的神经系统中表达最为明显;(5)两个具有不同组织活性的启动子驱动肝素酶的表达;(6)Oct 结合转录因子可能调节早期胚胎中肝素酶启动子的活性。这些数据表明,肝素酶在发育过程中广泛表达,但定位和水平受到精细调控。