Prexl Andrea, Münder Sandra, Loy Bernhard, Kremmer Elisabeth, Tischer Susanne, Böttger Angelika
Department of Biology 2, Ludwig-Maximilians-Universität München, Munich, Germany.
BMC Cell Biol. 2011 Sep 7;12:38. doi: 10.1186/1471-2121-12-38.
The Notch signalling pathway is conserved in pre-bilaterian animals. In the Cnidarian Hydra it is involved in interstitial stem cell differentiation and in boundary formation during budding. Experimental evidence suggests that in Hydra Notch is activated by presenilin through proteolytic cleavage at the S3 site as in all animals. However, the endogenous ligand for HvNotch has not been described yet.
We have cloned a cDNA from Hydra, which encodes a bona-fide Notch ligand with a conserved domain structure similar to that of Jagged-like Notch ligands from other animals. Hyjagged mRNA is undetectable in adult Hydra by in situ hybridisation but is strongly upregulated and easily visible at the border between bud and parent shortly before bud detachment. In contrast, HyJagged protein is found in all cell types of an adult hydra, where it localises to membranes and endosomes. Co-localisation experiments showed that it is present in the same cells as HvNotch, however not always in the same membrane structures.
The putative Notch ligand HyJagged is conserved in Cnidarians. Together with HvNotch it may be involved in the formation of the parent-bud boundary in Hydra. Moreover, protein distribution of both, HvNotch receptor and HyJagged indicate a more widespread function for these two transmembrane proteins in the adult hydra, which may be regulated by additional factors, possibly involving endocytic pathways.
Notch信号通路在两侧对称动物出现之前的动物中是保守的。在刺胞动物水螅中,它参与间充质干细胞分化以及出芽过程中的边界形成。实验证据表明,与所有动物一样,在水螅中Notch通过早老素在S3位点的蛋白水解切割而被激活。然而,HvNotch的内源性配体尚未被描述。
我们从水螅中克隆了一个cDNA,它编码一种真正的Notch配体,其保守结构域结构与来自其他动物的锯齿状Notch配体相似。通过原位杂交在成年水螅中检测不到Hyjagged mRNA,但在芽脱离前不久,在芽与亲体之间的边界处强烈上调且易于观察到。相比之下,HyJagged蛋白存在于成年水螅的所有细胞类型中,定位于细胞膜和内体。共定位实验表明,它与HvNotch存在于相同的细胞中,但并不总是存在于相同的膜结构中。
推测的Notch配体HyJagged在刺胞动物中是保守的。它与HvNotch一起可能参与水螅中亲体-芽边界的形成。此外,HvNotch受体和HyJagged的蛋白质分布表明这两种跨膜蛋白在成年水螅中具有更广泛的功能,这可能受其他因素调节,可能涉及内吞途径。