Watt F M
J Cell Biol. 1984 Jan;98(1):16-21. doi: 10.1083/jcb.98.1.16.
How terminally differentiating cells are selectively expelled from the basal layer of epidermis has been a source of interest and speculation for many years. The problem can now be studied in culture, using involucrin synthesis as an early marker of terminal differentiation in human keratinocytes. When keratinocytes are forced to grow as a monolayer by reducing the calcium ion concentration of the culture medium, they still begin to synthesize involucrin. Raising the level of calcium ions induces stratification, and cells that are synthesizing involucrin are selectively expelled from the basal layer. I have found that during calcium-induced stratification no new proteins or glycoproteins are synthesized, and the rate of cell division does not change. Movement of involucrin-positive cells out of the basal layer was found to be unaffected by cycloheximide, tunicamycin, or cytosine arabinoside. These results suggest that keratinocytes growing as a monolayer already have the necessary properties to determine their position when stratification is induced. Addition of calcium simply allows formation of desmosomes and other intimate cell contacts required for stratification. The properties of involucrin-positive cells that determine their suprabasal position include a reduced affinity for the culture substrate and preferential adhesion to other cells at the same stage of terminal differentiation. The molecular basis of these adhesive changes is discussed.
多年来，终末分化细胞如何从表皮基底层被选择性排出一直是人们感兴趣和猜测的来源。现在可以在培养中研究这个问题，使用兜甲蛋白合成作为人类角质形成细胞终末分化的早期标志物。当通过降低培养基中的钙离子浓度迫使角质形成细胞单层生长时，它们仍然开始合成兜甲蛋白。提高钙离子水平会诱导分层，并且正在合成兜甲蛋白的细胞会被选择性地从基底层排出。我发现，在钙诱导分层过程中，没有合成新的蛋白质或糖蛋白，细胞分裂速率也没有变化。发现兜甲蛋白阳性细胞从基底层移出不受环己酰亚胺、衣霉素或阿糖胞苷的影响。这些结果表明，单层生长的角质形成细胞已经具有在诱导分层时确定其位置所需的特性。添加钙仅仅允许形成分层所需的桥粒和其他紧密的细胞接触。决定其基底上层位置的兜甲蛋白阳性细胞的特性包括对培养底物的亲和力降低以及在终末分化的同一阶段对其他细胞的优先粘附。讨论了这些粘附变化的分子基础。
