Madison K C, Howard E J
Marshall Dermatology Research Laboratories, Department of Dermatology, University of Iowa, College of Medicine, Iowa City 52242, USA.
J Invest Dermatol. 1996 May;106(5):1030-5. doi: 10.1111/1523-1747.ep12338596.
The intercellular lipid sheets of the stratum corneum constitute the epidermal permeability barrier that permits terrestrial life. Although lamellar granules are known to deliver the precursors of the stratum corneum lipids into the intercellular spaces, their site of origin remains unknown. Lamellar granules have characteristics of both secretory granules and lysosomes, which are known to originate from the Golgi apparatus in other cell types. Glucosylceramides, a major component of lamellar granule contents and the precursors of stratum corneum ceramides, have been found to be synthesized primarily in the early compartments of the Golgi apparatus in other cell types. We have investigated the transport and metabolism of a fluorescently labeled ceramide in human keratinocyte cultures using laser-scanning confocal microscopy and lipid analysis. We found that ceramide is metabolized to glucosylceramide and sphingomyelin as it passes through the Golgi apparatus and the metabolites are then delivered to the plasma membrane. Cold temperature, Brefeldin A, and monensin, all known to inhibit transport from the Golgi to the plasma membrane, prevented ceramide metabolites from appearing at the plasma membrane. Because glucosylceramides are one of the most important lipid constituents of lamellar granules, these results support the hypothesis that the Golgi is the origin of lamellar granules.
角质层的细胞间脂质片层构成了允许陆地生物生存的表皮渗透屏障。尽管已知板层颗粒将角质层脂质的前体输送到细胞间隙中，但其起源部位仍然未知。板层颗粒具有分泌颗粒和溶酶体的特征，而在其他细胞类型中，这些已知起源于高尔基体。在其他细胞类型中，已发现葡糖神经酰胺是板层颗粒内容物的主要成分以及角质层神经酰胺的前体，主要在高尔基体的早期区室中合成。我们使用激光扫描共聚焦显微镜和脂质分析研究了荧光标记神经酰胺在人角质形成细胞培养物中的转运和代谢。我们发现，神经酰胺在通过高尔基体时会代谢为葡糖神经酰胺和鞘磷脂，然后这些代谢产物被输送到质膜。低温、布雷菲德菌素A和莫能菌素，所有这些都已知会抑制从高尔基体到质膜的转运，阻止了神经酰胺代谢产物出现在质膜上。由于葡糖神经酰胺是板层颗粒最重要的脂质成分之一，这些结果支持了高尔基体是板层颗粒起源的假说。
