The interaction of hyaluronate with the cell surface: the hyaluronate receptor and the core protein.

The interaction of hyaluronate with the cell surface: the hyaluronate receptor and the core protein.
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DOI:
10.1002/9780470513774.ch6
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发表时间:
2007-09
期刊:
Ciba Foundation symposium
影响因子:
--
通讯作者:
C. Underhill
C. Underhill
中科院分区:
其他
文献类型:
--
作者:
C. Underhill

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本文讨论了透明质酸与细胞表面相互作用的两种不同机制:首先,通过高亲和力结合透明质酸的受体;第二,通过一种与透明质酸共价连接的疏水蛋白。透明质酸受体是Mr 85,000的跨膜糖蛋白,似乎与细胞骨架的肌动蛋白丝相互作用。它识别透明质酸的六个糖残基序列,并以较低的亲和力与硫酸软骨素结合。在细胞表面,受体以合作的方式结合透明质酸,即两个或多个受体可以结合到相同的透明质酸分子上,从而产生高亲和力。单克隆抗体免疫组化染色表明该受体存在于上皮细胞、巨噬细胞和其他单核吞噬细胞以及某些类型的神经元中。在上皮细胞中,受体可能有助于介导细胞附着到通常富含透明质酸的基底膜上。该受体似乎也优先在增殖上皮细胞上表达,并可能作为某些类型癌症的标志物。巨噬细胞和相关细胞也有大量的受体,它可能在细胞迁移和/或细胞归巢到某些类型的组织中起作用。最近的研究表明,细胞表面透明质酸共价附着在膜相关的核心蛋白上。首先,如果用戊二醛固定培养的大鼠纤维肉瘤细胞,即使在预期会破坏非共价键的条件下,细胞表面透明质酸仍与细胞相关。其次,当细胞表面透明质酸与Triton X-114分开时,在疏水相中恢复了很大一部分,这表明它与疏水蛋白相连。最后,细胞表面透明质酸与硝化纤维素的结合似乎是通过与蛋白质的共价键介导的。
Two distinct mechanisms are discussed by which hyaluronate interacts with the surfaces of cells: first, through a receptor which binds to hyaluronate with high affinity; and second, through a hydrophobic protein which is covalently linked to hyaluronate. The hyaluronate receptor is a transmembrane glycoprotein of Mr 85,000 which appears to interact with actin filaments of the cytoskeleton. It recognizes a sequence of six sugar residues of hyaluronate and also binds to chondroitin sulphate with a lower affinity. On the cell surface the receptors bind hyaluronate in cooperative fashion whereby two or more receptors can bind to the same molecule of hyaluronate, resulting in a high affinity. Immunohistochemical staining with a monoclonal antibody to the receptor indicates that it is present on epithelia, macrophages and other mononuclear phagocytes as well as some type of neurons. In epithelia the receptors presumably help to mediate cell attachment to the basement membrane which is often rich in hyaluronate. The receptor also appears to be preferentially expressed on proliferating epithelial cells and may serve as a marker for some types of carcinomas. Macrophages and related cells also have large amounts of the receptor, where it may serve in cell migration and/or in the homing of the cells to certain types of tissues. Recent studies have suggested that cell surface hyaluronate is covalently attached to a membrane-associated core protein. First, if cultured rat fibrosarcoma cells are fixed with glutaraldehyde the cell surface hyaluronate remains associated with the cells even under conditions expected to break non-covalent bonds. Second, when cell surface hyaluronate is partitioned with Triton X-114 a significant fraction is recovered in the hydrophobic phase, suggesting attachment to a hydrophobic protein. And finally, the binding of cell surface hyaluronate to nitrocellulose appears to be mediated through a covalent linkage to a protein.