Biochemistry. Walking on solid ground.
Biochemistry. Walking on solid ground.
复制标题
生物化学。在坚实的地面上行走。
DOI：
10.1126/science.1227091
复制
发表时间：
2012-08-24
期刊：
影响因子：
--
通讯作者：
Dickey BF
中科院分区：
文献类型：
--
作者：
Dickey BF
整个身体的粘液表面，包括呼吸道、胃肠道和泌尿生殖道的粘液表面，是湿上皮细胞，在其防御中包括某种形式的粘液凝胶。值得注意的是，气道粘膜通过纤毛搏动将其粘液凝胶层推出肺部（图A，B），从而快速清除吸入的病原体和有毒物质（1）。传统的模型是粘液凝胶层位于睫状体周围液层的顶部。由于粘液凝胶的密度比水大，因此假设它通过纤毛的跳动保持悬浮。然而，正如巴顿等人在本期《科学》杂志上所报道的那样（2），这个模型从根本上是错误的，现在显示，睫状体层含有一个大分子结构，其网孔尺寸小于移动的凝胶层的网孔尺寸，并且相应地具有更大的渗透模量。技术，以及运动纤毛应该在流体中运动得最好的直觉。最近的形态学研究显示，纤毛周层中有一个密集的大分子网络，从纤毛、微绒毛和顶端细胞膜的表面发出（2，3）。该网络的结构和免疫组织化学特征与其主要由通过跨膜结构域束缚于细胞表面的特定粘蛋白以及更靠近细胞表面的束缚粘多糖组成一致（4）。粘蛋白是一种大的、高度糖基化的蛋白质。由于带电荷的糖部分相互排斥，膜系粘蛋白很可能采用延伸的构型，如从细胞表面突出的瓶刷（图C，D）。这导致了一个模型，其中纤毛周围层可以被认为是一个粘液凝胶移植到细胞表面。
Mucosal surfaces throughout the body, including those of the respiratory, gastrointestinal, and genitourinary tracts, are wet epithelia that include some form of mucus gel among their defenses. The airway mucosa is notable for the propulsion of its mucus gel layer out of the lungs by ciliary beating (Figure A, B), allowing for the rapid removal of inhaled pathogens and toxicants (1). The conventional model has been that the mucus gel layer lies atop a periciliary fluid layer. Since the mucus gel is denser than water, it was hypothesized to be kept suspended by the beating of cilia. However, as reported by Button et al. in this issue of Science (2), this model turns out to be fundamentally wrong, with the periciliary layer now shown to contain a macromolecular structure with a mesh size smaller than that of the mobile gel layer and a correspondingly greater osmotic modulus.The incorrect impression of a fluid periciliary layer seems to have derived from the lack of visible ultrastructure using older fixation techniques, together with the intuitive sense that motile cilia should move best in a fluid. More recent morphologic studies reveal a dense network of macromolecules in the periciliary layer, emanating from the surface of cilia, microvilli and apical cell membranes (2, 3). Structural and immunohistochemical characteristics of this network are consistent with it being composed primarily of particular mucins tethered to the cell surface by transmembrane domains, as well as tethered mucopolysaccharides closer to the cell surface (4). Mucins are large, heavily glycosylated proteins. Since the charged sugar moieties repel each other, membrane-tethered mucins are likely to adopt an extended configuration like bottle brushes protruding from the cell surface (Figure C, D). This leads to a model in which the periciliary layer can be conceived as a mucus gel grafted onto the cell surface.
登录
查看更多内容
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1126/science.1223012
发表时间：
2012-08-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Button B;Cai LH;Ehre C;Kesimer M;Hill DB;Sheehan JK;Boucher RC;Rubinstein M
通讯作者：
Rubinstein M
DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
影响因子：
4.8
作者：
Raynal, BDE;Hardingham, TE;Thornton, DJ
通讯作者：
Thornton, DJ
DOI：
10.1084/jem.20120562
发表时间：
2012-07-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gustafsson JK;Ermund A;Ambort D;Johansson ME;Nilsson HE;Thorell K;Hebert H;Sjövall H;Hansson GC
通讯作者：
Hansson GC