Regulation of cell adhesion by polysialic acid
Regulation of cell adhesion by polysialic acid
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DOI：
10.1074/jbc.m104525200
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发表时间：
2001-08-24
影响因子：
4.8
通讯作者：
Rutishauser, U
中科院分区：
文献类型：
--
作者：
Fujimoto, I;Bruses, JL;Rutishauser, U
神经细胞粘附分子（NCAM）的多唾液酸化在脊椎动物中进化，以执行与细胞位置和形态变化相关的生物学功能。其中许多效应涉及细胞相互作用的减弱，而这些相互作用不是通过 NCAM 自身的粘附特性介导的。这种对细胞相互作用的整体影响的拟议机制是仅基于聚唾液酸（PSA）生物物理特性的膜-膜并置的空间抑制。然而，NCAM 多肽的内在结合或信号传导特性仍然可能也参与其中。为了帮助解决这个问题，本研究使用定量细胞分离测定以及经过工程改造的细胞，以显示不同的粘附受体以及各种多聚唾液酸化的 NCAM 多肽亚型和功能域缺失突变。获得的结果表明，PSA 的调节发生在 IgCAM、钙粘蛋白和整联蛋白等多种粘附受体上，并且除了聚唾液酸化最低限度所需的功能域外，不需要 NCAM 功能域。这些发现与 PSA 作用的细胞附着机制最为一致，因为该模型预测 PSA-NCAM 对细胞粘附的抑制作用应该独立于粘附系统的性质以及 NCAM 多肽本身的任何内在结合或信号传导特性。
The polysialylation of neural cell adhesion molecule (NCAM) evolved in vertebrates to carry out biological functions related to changes in cell position and morphology. Many of these effects involve the attenuation of cell interactions that are not mediated through NCAM's own adhesion properties. A proposed mechanism for this global effect on cell interaction is the steric inhibition of membrane-membrane apposition based solely on polysialic acid (PSA) biophysical properties. However, it remains possible that the intrinsic binding or signaling properties of the NCAM polypeptide are also involved. To help resolve this issue, this study uses a quantitative cell detachment assay together with cells engineered to display different adhesion receptors together with a variety of polysialylated NCAM polypeptide isoforms and functional domain deletion mutations. The results obtained indicate that regulation by PSA occurs with adhesion receptors as diverse as an IgCAM, a cadherin and an integrin, and does not require NCAM functional domains other than those minimally required for polysialylation. These findings are most consistent with the cell apposition mechanism for PSA action, as this model predicts that the inhibitory effects of PSA-NCAM on cell adhesion should be independent of the nature of the adhesion system and of any intrinsic binding or signalling properties of the NCAM polypeptide itself.