Lorenz Katrin, Grashoff Carsten, Torka Robert, Sakai Takao, Langbein Lutz, Bloch Wilhelm, Aumailley Monique, Fässler Reinhard
Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
J Cell Biol. 2007 May 7;177(3):501-13. doi: 10.1083/jcb.200608125.
Integrin-linked kinase (ILK) links integrins to the actin cytoskeleton and is believed to phosphorylate several target proteins. We report that a keratinocyte-restricted deletion of the ILK gene leads to epidermal defects and hair loss. ILK-deficient epidermal keratinocytes exhibited a pronounced integrin-mediated adhesion defect leading to epidermal detachment and blister formation, disruption of the epidermal-dermal basement membrane, and the translocation of proliferating, integrin-expressing keratinocytes to suprabasal epidermal cell layers. The mutant hair follicles were capable of producing hair shaft and inner root sheath cells and contained stem cells and generated proliferating progenitor cells, which were impaired in their downward migration and hence accumulated in the outer root sheath and failed to replenish the hair matrix. In vitro studies with primary ILK-deficient keratinocytes attributed the migration defect to a reduced migration velocity and an impaired stabilization of the leading-edge lamellipodia, which compromised directional and persistent migration. We conclude that ILK plays important roles for epidermis and hair follicle morphogenesis by modulating integrin-mediated adhesion, actin reorganization, and plasma membrane dynamics in keratinocytes.
整合素连接激酶（ILK）将整合素与肌动蛋白细胞骨架相连，并被认为可使多种靶蛋白磷酸化。我们报道，ILK基因在角质形成细胞中的特异性缺失会导致表皮缺陷和脱发。ILK缺陷的表皮角质形成细胞表现出明显的整合素介导的黏附缺陷，导致表皮脱离和水疱形成、表皮-真皮基底膜破坏，以及增殖的、表达整合素的角质形成细胞向表皮上层细胞层移位。突变的毛囊能够产生毛干和内根鞘细胞，含有干细胞并产生增殖的祖细胞，这些祖细胞向下迁移受损，因此积聚在外根鞘中，无法补充毛基质。对原代ILK缺陷角质形成细胞的体外研究将迁移缺陷归因于迁移速度降低和前沿板状伪足稳定性受损，这损害了定向和持续迁移。我们得出结论，ILK通过调节角质形成细胞中整合素介导的黏附、肌动蛋白重组和质膜动力学，在表皮和毛囊形态发生中发挥重要作用。
