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基底膜蛋白:结构、组装及细胞相互作用

Basement membrane proteins: structure, assembly, and cellular interactions.

作者信息

Paulsson M

机构信息

M. E. Müller-Institute for Biomechanics, University of Bern, Switzerland.

出版信息

Crit Rev Biochem Mol Biol. 1992;27(1-2):93-127. doi: 10.3109/10409239209082560.

DOI:10.3109/10409239209082560
PMID:1309319
Abstract

Basement membranes are thin layers of a specialized extracellular matrix that form the supporting structure on which epithelial and endothelial cells grow, and that surround muscle and fat cells and the Schwann cells of peripheral nerves. One common denominator is that they are always in close apposition to cells, and it has been well demonstrated that basement membranes do not only provide a mechanical support and divide tissues into compartments, but also influence cellular behavior. The major molecular constituents of basement membranes are collagen IV, laminin-entactin/nidogen complexes, and proteoglycans. Collagen IV provides a scaffold for the other structural macromolecules by forming a network via interactions between specialized N- and C-terminal domains. Laminin-entactin/nidogen complexes self-associate into less-ordered aggregates. These two molecular assemblies appear to be interconnected, presumably via binding sites on the entactin/nidogen molecule. In addition, proteoglycans are anchored into the membrane by an unknown mechanism, providing clusters of negatively charged groups. Specialization of different basement membranes is achieved through the presence of tissue-specific isoforms of laminin and collagen IV and of particular proteoglycan populations, by differences in assembly between different membranes, and by the presence of accessory proteins in some specialized basement membranes. Many cellular responses to basement membrane proteins are mediated by members of the integrin class of transmembrane receptors. On the intracellular side some of these signals are transmitted to the cytoskeleton, and result in an influence on cellular behavior with respect to adhesion, shape, migration, proliferation, and differentiation. Phosphorylation of integrins plays a role in modulating their activity, and they may therefore be a part of a more complex signaling system.

摘要

基底膜是一层薄薄的特殊细胞外基质,它形成上皮细胞和内皮细胞生长的支撑结构,环绕肌肉、脂肪细胞以及周围神经的施万细胞。一个共同特征是它们总是与细胞紧密相邻,并且已经充分证明基底膜不仅提供机械支撑并将组织分隔成不同区域,还会影响细胞行为。基底膜的主要分子成分是IV型胶原蛋白、层粘连蛋白-巢蛋白/内动蛋白复合物和蛋白聚糖。IV型胶原蛋白通过特殊的N端和C端结构域之间的相互作用形成网络,为其他结构大分子提供支架。层粘连蛋白-巢蛋白/内动蛋白复合物自我缔合形成无序程度较低的聚集体。这两种分子组装似乎相互连接,可能是通过巢蛋白/内动蛋白分子上的结合位点。此外,蛋白聚糖通过一种未知机制锚定在膜中,提供带负电荷的基团簇。不同基底膜的特化是通过层粘连蛋白和IV型胶原蛋白的组织特异性异构体以及特定蛋白聚糖群体的存在、不同膜之间组装方式的差异以及一些特殊基底膜中辅助蛋白的存在来实现的。许多细胞对基底膜蛋白的反应是由跨膜受体整合素家族的成员介导的。在细胞内侧,其中一些信号会传递到细胞骨架,并对细胞在黏附、形状、迁移、增殖和分化方面的行为产生影响。整合素的磷酸化在调节其活性方面发挥作用,因此它们可能是更复杂信号系统的一部分。

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