Surface relocation of alpha 6 beta 4 integrins and assembly of hemidesmosomes in an in vitro model of wound healing.
Surface relocation of alpha 6 beta 4 integrins and assembly of hemidesmosomes in an in vitro model of wound healing.
复制标题
Alpha 6β4整合素的表面迁移和在伤口愈合模型中的半底体组装。
DOI：
10.1083/jcb.115.6.1737
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发表时间：
1991-12
影响因子：
7.8
通讯作者：
Jones, J C
中科院分区：
文献类型：
--
作者：
Kurpakus, M A;Quaranta, V;Jones, J C
整联蛋白家族的跨膜细胞外基质受体 α 6 β 4 是半桥粒的组成部分，半桥粒是上皮细胞结缔组织附着中重要的粘附复合物（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，和 V.Quaranta，1991。细胞调节。半桥粒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) 的 125-kD 成分和含有 VII 型胶原的锚定原纤维。我们在体外伤口愈合外植体模型中监测了 α 6 β 4 整合素并入形成半桥粒的情况。在最近从未受伤部位边缘迁移到裸露结缔组织上的上皮细胞中，α6β4首先沿着整个细胞表面出现。在此阶段，这些细胞含有很少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，而它们已经对层粘连蛋白和 CAF 呈阳性。在后期，当细胞对胞浆半桥粒成分（如 BP 抗原和 VII 型胶原）呈阳性时，α 6 β 4 沿着上皮细胞的基底极集中，与外植体的结缔组织邻接。 β4 多克隆抗体不会干扰外植体中上皮细胞的迁移。然而，它们会阻止半桥粒复合物的组装，并抑制迁移到伤口区域的细胞中 VII 型胶原蛋白的表达。此外，它们还诱导外植体未受伤区域的非迁移细胞中已建立的半桥粒的破坏。 α6 的单克隆抗体具有更显着的效果，因为它们可以完全分离外植体未受伤区域的上皮细胞。 CAF 抗体也会使未受伤区域的上皮细胞分离，显然是通过诱导基底膜区透明层上皮和结缔组织之间的分离。这些结果提出了一种模型，通过α 6 β 4 极化到细胞基底表面（可能是由假定的锚定丝相关配体诱导），触发半桥粒斑块的组装。
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.