Fox J E, Boyles J K, Berndt M C, Steffen P K, Anderson L K
Department of Pathology, Gladstone Foundation Laboratories for Cardiovascular Disease, University of California, San Francisco 94140-0608.
J Cell Biol. 1988 May;106(5):1525-38. doi: 10.1083/jcb.106.5.1525.
Platelets have previously been shown to contain actin filaments that are linked, through actin-binding protein, to the glycoprotein (GP) Ib-IX complex, GP Ia, GP IIa, and an unidentified GP of Mr 250,000 on the plasma membrane. The objective of the present study was to use a morphological approach to examine the distribution of these membrane-bound filaments within platelets. Preliminary experiments showed that the Triton X-100 lysis buffers used previously to solubilize platelets completely disrupt the three-dimensional organization of the cytoskeletons. Conditions were established that minimized these postlysis changes. The cytoskeletons remained as platelet-shaped structures. These structures consisted of a network of long actin filaments and a more amorphous layer that outlined the periphery. When Ca2+ was present, the long actin filaments were lost but the amorphous layer at the periphery remained; conditions were established in which this amorphous layer retained the outline of the platelet from which it originated. Immunocytochemical experiments showed that the GP Ib-IX complex and actin-binding protein were associated with the amorphous layer. Analysis of the amorphous material on SDS-polyacrylamide gels showed that it contained actin, actin-binding protein, and all actin-bound GP Ib-IX. Although actin filaments could not be visualized in thin section, the actin presumably was in a filamentous form because it was solubilized by DNase I and bound phalloidin. These studies show that platelets contain a membrane skeleton and suggest that it is distinct from the network of cytoplasmic actin filaments. This membrane skeleton exists as a submembranous lining that, by analogy to the erythrocyte membrane skeleton, may stabilize the plasma membrane and contribute to determining its shape.
此前已表明,血小板含有肌动蛋白丝,这些肌动蛋白丝通过肌动蛋白结合蛋白与糖蛋白(GP)Ib-IX复合物、GP Ia、GP IIa以及质膜上一个分子量为250,000的未鉴定糖蛋白相连。本研究的目的是采用形态学方法检查这些膜结合丝在血小板内的分布。初步实验表明,先前用于溶解血小板的Triton X-100裂解缓冲液会完全破坏细胞骨架的三维结构。已确定了能将这些裂解后变化降至最低的条件。细胞骨架仍保留血小板形状的结构。这些结构由长肌动蛋白丝网络和勾勒周边的更无定形层组成。当存在Ca2+时,长肌动蛋白丝消失,但周边的无定形层仍保留;已确定了这样的条件,即该无定形层保留了其起源血小板的轮廓。免疫细胞化学实验表明,GP Ib-IX复合物和肌动蛋白结合蛋白与无定形层相关。对SDS-聚丙烯酰胺凝胶上的无定形物质进行分析表明,它含有肌动蛋白、肌动蛋白结合蛋白以及所有与肌动蛋白结合的GP Ib-IX。尽管在薄切片中无法看到肌动蛋白丝,但推测肌动蛋白呈丝状,因为它可被DNase I溶解并与鬼笔环肽结合。这些研究表明,血小板含有膜骨架,并提示它与细胞质肌动蛋白丝网络不同。这种膜骨架作为膜下衬里存在,类似于红细胞膜骨架,可能稳定质膜并有助于确定其形状。