Studies of human genetic disorders and animal models indicate that matriptase plays essential roles in proteolytic processes associated with profilaggrin processing and desquamation at late stages of epidermal differentiation. The tissue distribution profile and zymogen activation status in human skin, however, suggests that matriptase physiological function in the skin more likely lies in the proliferating and differentiating keratinocytes in the basal and spinous layers. Marked acanthosis with expanded spinous layer and lack of significant changes in intensity and expression pattern for several terminal differentiation markers in the skin of ARIH patients support matriptase’s role in earlier rather than the later stages of differentiation. In addition to the tissue distribution, differential subcellular localization further limits the ability of extracellular matriptase proteolytic activity to access the cytosolic non-membrane-bound keratohyalin granules, in which profilaggrin processing occurs. The short lifespan of active matriptase, which results from tightly controlled zymogen activation, rapid inhibition by HAI-1, and shedding from cell surface, indicates that active matriptase likely performs physiological functions via limited proteolysis on its substrates, as needed, rather than via a continuous bulk process. We, here, review these spatiotemporal controls of matriptase proteolytic activity at the biochemical, cellular, and tissue level. Based on this in-depth understanding of how matriptase activity is regulated, we argue that there is no direct involvement of matriptase proteolytic activity in profilaggrin processing and desquamation. The defects in epidermal terminal differentiation associated with matriptase deficiency are likely secondary and are due to putative disruption at earlier stages of differentiation.

中文翻译：

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时空控制人Matriptase在其生理底物上的作用：反对在Profilaggrin加工和脱皮中Matriptase蛋白水解活性直接作用的案例。

对人类遗传疾病和动物模型的研究表明，在表皮分化的后期，麦芽糖磷酸酶在与proprolaggrin加工和脱皮有关的蛋白水解过程中起着至关重要的作用。然而，人皮肤中的组织分布图和酶原活化状态表明，皮肤中的脱氧核糖核酸酶生理功能更可能在于基底层和棘层中增殖和分化的角质形成细胞。ARIH患者皮肤中的几个棘突分化标志物棘突具有扩展的棘突层，并且强度和表达模式没有明显变化，这支持了matriptase在分化的早期而不是后期的作用。除了组织分布 差异性亚细胞定位进一步限制了细胞外matriptase蛋白水解活性访问胞质中非膜结合的角蛋白透明质颗粒的能力，在其中发生前纤蛋白加工。活化的Matriptase的寿命短，是由于严格控制的酶原激活，HAI-1的快速抑制以及从细胞表面脱落造成的，这表明，根据需要，活化的Matriptase可能通过有限的蛋白水解作用来发挥生理功能，而不是通过连续批量过程。在这里，我们回顾了在生化，细胞和组织水平上这些对脂蛋白水解酶活性的时空控制。基于对MATP酶活性如何调控的深入了解，我们认为，麦芽糖蛋白酶的蛋白水解活性与原丝蛋白的加工和脱皮没有直接关系。与matriptase缺乏症相关的表皮终末分化缺陷可能是继发性的，并且归因于分化早期的假定破坏。