Morel Etienne, Demignot Sylvie, Chateau Danielle, Chambaz Jean, Rousset Monique, Delers François
Unité Mixte de Recherche, Institut National de la Santé et de la Recherche Médicale U505, Université Pierre et Marie Curie, Laboratoire de Pharmacologie Cellulaire et Moléculaire de l'EPHE, 75006 Paris, France.
Mol Biol Cell. 2004 Jan;15(1):132-41. doi: 10.1091/mbc.e03-04-0215. Epub 2003 Oct 17.
Enterocytes are highly polarized cells that transfer nutrients across the intestinal epithelium from the apical to the basolateral pole. Apolipoprotein B (apoB) is a secretory protein that plays a key role in the transepithelial transport of dietary fatty acids as triacylglycerol. The evaluation of the control of apoB traffic by lipids is therefore of particular interest. To get a dynamic insight into this process, we used the enterocytic Caco-2 cells cultured on microporous filters, a system in which the apical and basal compartments can be delimited. Combining biochemical and morphological approaches, our results showed that, besides their role in protection from degradation, lipids control the intracellular traffic of apoB in enterocytes. A supply of fatty acids and cholesterol is sufficient for the export of apoB from the endoplasmic reticulum and its post-Golgi traffic up to the apical brush-border domain, where it remains until an apical supply of complex lipid micelles signals its chase down to the basolateral secretory domain. This downward traffic of apoB involves a microtubule-dependent process. Our results demonstrate an enterocyte-specific bidirectional process for the lipid-dependent traffic of a secretory protein.
肠上皮细胞是高度极化的细胞，可将营养物质从肠上皮的顶端跨上皮转运至基底外侧极。载脂蛋白B（apoB）是一种分泌蛋白，在膳食脂肪酸作为三酰甘油的跨上皮转运中起关键作用。因此，评估脂质对apoB转运的控制尤为重要。为了深入动态了解这一过程，我们使用了在微孔滤膜上培养的肠上皮Caco-2细胞，该系统中顶端和基底部分可以界定。结合生化和形态学方法，我们的结果表明，脂质除了具有防止降解的作用外，还控制肠上皮细胞中apoB的细胞内转运。脂肪酸和胆固醇的供应足以使apoB从内质网输出，并在高尔基体后转运至顶端刷状缘结构域，在那里它会一直停留，直到顶端供应复合脂质微团信号将其追踪至基底外侧分泌结构域。apoB的这种向下转运涉及一个微管依赖过程。我们的结果证明了分泌蛋白脂质依赖性转运的肠上皮细胞特异性双向过程。
