Institute of Molecular and Cellular Anatomy, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany.
Institute of Molecular and Cellular Anatomy, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany.
J Invest Dermatol. 2019 Sep;139(9):1876-1888.e4. doi: 10.1016/j.jid.2019.03.1139. Epub 2019 Apr 2.
Hemidesmosomes anchor the epidermal keratin filament cytoskeleton to the extracellular matrix. They are crucial for the mechanical integrity of skin. Their role in keratinocyte migration, however, remains unclear. Examining migrating primary human keratinocytes, we find that hemidesmosomes cluster as ordered arrays consisting of multiple chevrons that are flanked by actin-associated focal adhesions. These hemidesmosomal arrays with intercalated focal adhesions extend from the cell rear to the cell front. New hemidesmosomal chevrons form subsequent to focal adhesion assembly at the cell's leading front, whereas chevrons and associated focal adhesions disassemble at the cell rear in reverse order. The bulk of the hemidesmosome-focal adhesion composite, however, remains attached to the substratum during cell translocation. Similar hemidesmosome-focal adhesion patterns emerge on X-shaped fibronectin-coated micropatterns, during cell spreading and in leader cells during collective cell migration. We further find that hemidesmosomes and focal adhesions affect each other's distribution. We propose that both junctions are separate but linked entities, which treadmill coordinately to support efficient directed cell migration and cooperate to coordinate the dynamic interplay between the keratin and actin cytoskeleton.
半桥粒将表皮角蛋白丝细胞骨架锚定到细胞外基质。它们对半桥粒在角蛋白细胞迁移中的作用至关重要。然而，它们在角蛋白细胞迁移中的作用仍不清楚。在研究迁移的原代人角质形成细胞时，我们发现半桥粒簇集形成由多个楔形物组成的有序排列，楔形物两侧是与肌动蛋白相关的黏着斑。这些带有穿插黏着斑的半桥粒阵列从细胞后端延伸到细胞前端。在细胞前缘形成新的黏着斑后，楔形物和相关的黏着斑在细胞后端以相反的顺序解体。然而，在细胞迁移过程中，大部分半桥粒-黏着斑复合物仍附着在基质上。在 X 形纤维连接蛋白包被的微图案上，细胞扩展过程中和集体细胞迁移过程中的先导细胞中，也出现了类似的半桥粒-黏着斑模式。我们进一步发现半桥粒和黏着斑会影响彼此的分布。我们提出，这两个连接点是独立但相关的实体，它们协同地协调，以支持有效的定向细胞迁移，并协同合作，协调角蛋白和肌动蛋白细胞骨架之间的动态相互作用。
