A transmembrane extracellular matrix receptor of the integrin family, alpha 6 beta 4, is a component of the hemidesmosome, an adhesion complex of importance in epithelial cell-connective tissue attachment (Stepp, M. A., S. Spurr-Michaud, A. Tisdale, J. Elwell, and I. K. Gipson. 1990. Proc. Natl. Acad. Sci. USA. 87:8970-8974; Jones, J. C. R., M. A. Kurpakus, H. M. Cooper, and V. Quaranta. 1991. Cell Regulation. 2:427-438). Cytosolic components of hemidesmosomes include bullous pemphigoid (BP) antigens while extracellular components include a 125-kD component of anchoring filaments (CAF) and collagen type VII-containing anchoring fibrils. We have monitored the incorporation of the alpha 6 beta 4 integrins into forming hemidesmosomes in an in vitro wound-healing explant model. In epithelial cells recently migrated from the edges of unwounded sites over bare connective tissue, alpha 6 beta 4 first appears along the entire cell surface. At this stage, these cells contain little or no cytosolic hemidesmosomal components, at least as detectable by immunofluorescence using BP autoantibodies, whereas they are already positive for laminin and CAF. At a later stage, as cells become positive for cytosolic hemidesmosome components such as BP antigens as well as collagen type VII, alpha 6 beta 4 becomes concentrated along the basal pole of the epithelial cell where it abuts the connective tissue of the explant. Polyclonal antibodies to beta 4 do not interfere with the migration of epithelial cells in the explant. However, they prevent assembly of hemidesmosomal complexes and inhibit expression of collagen type VII in cells that have migrated over wound areas. In addition, they induce disruption of established hemidesmosomes in nonmigrating cells of the unwounded area of the explant. Monoclonal antibodies to alpha 6 have a more dramatic effect, since they completely detach epithelial cells in the unwounded area of the explant. Antibodies to CAF also detach epithelial cells in unwounded areas, apparently by inducing separation between epithelium and connective tissue at the lamina lucida of the basement membrane zone. These results suggest a model whereby polarization of alpha 6 beta 4 to the basal surface of the cells, perhaps induced by a putative anchoring filament-associated ligand, triggers assembly of hemidesmosome plaques.

译文

:整联蛋白家族的跨膜细胞外基质受体,α6 beta 4,是半桥粒的成分,半桥粒是在上皮细胞结缔组织附着中重要的粘附复合物(Stepp,MA,S。Spurr-Michaud,A。Tisdale, J. Elwell和IK Gipson。1990.美国国家科学院院刊87:8970-8974; Jones,JCR,MA Kurpakus,HM Cooper和V.Quaranta。1991.《细胞调节》 2:427- 438)。血小体的胞质成分包括大疱性类天疱疮(BP)抗原,而细胞外成分包括锚定丝(CAF)和含VII型胶原的锚定纤丝的125 kD成分。我们已经监测了在体外伤口愈合的外植体模型中将α6β4整合素整合到形成hemidemosomes中。在最近从裸结缔组织上方未受伤部位边缘迁移的上皮细胞中,α6 beta 4首先沿整个细胞表面出现。在这一阶段,这些细胞几乎不含有或不含胞质半桥粒成分,至少可以通过使用BP自身抗体的免疫荧光检测到,而对于层粘连蛋白和CAF则已经呈阳性。在稍后的阶段,随着细胞对胞质半桥体成分(例如BP抗原)和VII型胶原呈阳性,α6β4沿着上皮细胞的基极集中,并与外植体的结缔组织邻接。针对β4的多克隆抗体不会干扰外植体中上皮细胞的迁移。然而,它们阻止了半桥粒复合物的组装并抑制了在伤口区域上迁移的细胞中VII型胶原的表达。另外,它们在外植体未受伤区域的非迁移细胞中诱导已建立的半染色体的破坏。针对α6的单克隆抗体具有更引人注目的效果,因为它们可以完全脱离外植体未受伤区域中的上皮细胞。 CAF抗体还可以在未受伤的区域分离上皮细胞,这显然是通过诱导基底膜区域的透明层上皮与结缔组织之间的分离来实现的。这些结果表明了一个模型,其中α6β4极化到细胞的基底表面(可能是由假定的锚定细丝相关配体诱导的)触发了半血球斑块的组装。

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