先前此蛋白质家族，存在于血管前端，会与两个蛋白质受器相结合。此次则发现Sema3E 只与一个 neuropilin 蛋白质受器相结合，利用不同方式发挥功用。
Gu 和 Alex Kolodkin 博士、和 David Ginty 博士等人，在分析经修饰带蓝色的 Sema3E 和其受器后发现，其形式与先前发现于血管和神经的 plexin-D1 蛋白质相似。他们将 plexin-D1 插入不含此蛋白质的猴子细胞内；结果发现 Sema3E 能与此细胞紧密结合，并产生讯号。
为了了解此三个蛋白质对血管形成的影响，Gu 和 Yutaka Yoshida 博士等人，利用缺乏此些蛋白质的老鼠进行研究，结果发现，老鼠缺乏 Sema3E 或 plexin-D1 时，血管无法形成。然而缺乏第三种蛋白质 neuropilin 时，血管仍可正常形成。
Sema3E 最初自肿瘤细胞所分得，可能与癌症发展有关。目前已可在包括人类等许多生物体内发现 plexin-D1 和 Sema3E；其受损时会导致血管生育缺陷、冠状心脏疾病、和成年神经退化等问题。
New Protein 'Stop Sign' Alters Blood Vessel Growth
In experiments with mice, a research team led by Johns Hopkins scientists has discovered an unusual protein pair that stops blood vessels' growth in the developing back. Results of the studies, published today in the express online edition of Science, are of special interest to researchers trying to prevent blood flow that nourishes tumors or exploit the signals vessels emit during growth to help regrow damaged nerves.
During an animal's prenatal development, protein "signs" tell growing blood vessels which way to go and when to stop or turn back. Scientists already knew that one big family of "stop" proteins works by binding to two proteins, called receptors, on the leading edge of a budding blood vessel. In new experiments, the Hopkins-led team reports on one member of this family of proteins that works differently from the others.
"Unlike all of the others in this group, called semaphorins, this protein only needs one protein receptor partner," says lead author Chenghua Gu, D.V.M., Ph.D., a postdoctoral fellow in neuroscience in Hopkins' Institute for Basic Biomedical Sciences. "It's a totally new observation of blood vessel growth in development, and it has made us rethink how the semaphorins control this process."
Semaphorins float freely in tissues adjacent to blood vessels and nerves and stop them from migrating into inappropriate areas. Although the protein the team studied, known as Sema3E, belongs to this family, its binding partners and exact job were unclear until now.
Gu and others from the laboratories of Hopkins neuroscience professors Alex Kolodkin, Ph.D., and David Ginty, Ph.D., engineered a version of Sema3E that colors its binding partner blue. They found that the resulting blue pattern on the developing mice looked suspiciously like the pattern of plexin-D1, a previously described protein found in blood vessels and nerves.
To prove that this was indeed Sema3E's binding partner, the researchers inserted the plexin-D1 protein into cultured monkey cells that don't naturally contain it. They discovered that the Sema3E protein bound tightly to the monkey cells and created a signal. Surprisingly, the two proteins didn't need a third that is known to work with semaphorins in other situations.
To see how each of these three proteins affects blood vessel migration, Gu and colleagues from Hopkins, Yutaka Yoshida, Ph.D., and other collaborators from Columbia University and the Developmental Biology Institute of Marseille in France engineered mice to lack each of the three proteins. In mice without Sema3E or plexin-D1, blood vessels along a particular part of the back were disorganized. In contrast, mice lacking the third protein (called neuropilin) grew the vessels normally.
"We know that these two proteins are crucial for the growth of blood vessels in the back, but now we're investigating whether the pair controls blood vessels and nerves in other parts of the developing mouse, too," says Ginty, also a Howard Hughes Medical Institute investigator.
Sema3E was originally isolated from an invasive tumor cell line, so it's thought to be associated with progression of cancer. Both plexin-D1 and Sema3E are found in many species, including humans, and when disrupted could contribute to vascular birth defects, coronary heart disease, and adult nerve regeneration problems, say the researchers.
This research was supported by grants from the National Institutes of Health (NIH), Howard Hughes Medical Institute (HHMI), the Christopher Reeve Paralysis Foundation, the Packard Center for ALS Research at Johns Hopkins, the Institut National de la Santé et de la Recherche Médical (INSERM), Centre National de la Recherche Scientifique (CNRS), Association Fran?aise contre les Myopathies (AFM) and a European Commission contract.
作者:admin@医学,生命科学 2011-09-17 06:36