Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden.
Nat Cell Biol. 2010 Nov;12(11):1071-7. doi: 10.1038/ncb2111. Epub 2010 Oct 10.
Iron is an essential element in many biological processes. In vertebrates, serum transferrin is the major supplier of iron to tissues, but the function of additional transferrin-like proteins remains poorly understood. Melanotransferrin (MTf) is a phylogenetically conserved, iron-binding epithelial protein. Elevated MTf levels have been implicated in melanoma pathogenesis. Here, we present a functional analysis of MTf in Drosophila melanogaster. Similarly to its human homologue, Drosophila MTf is a lipid-modified, iron-binding protein attached to epithelial cell membranes, and is a component of the septate junctions that form the paracellular permeability barrier in epithelial tissues. We demonstrate that septate junction assembly during epithelial maturation relies on endocytosis and apicolateral recycling of iron-bound MTf. Mouse MTf complements the defects of Drosophila MTf mutants. Drosophila provides the first genetic model for the functional dissection of MTf in epithelial junction assembly and morphogenesis.
铁是许多生物过程中的必需元素。在脊椎动物中，血清转铁蛋白是向组织提供铁的主要物质，但其他类似转铁蛋白的功能仍知之甚少。黑素转铁蛋白（MTf）是一种进化上保守的、与铁结合的上皮蛋白。升高的 MTf 水平与黑色素瘤的发病机制有关。在这里，我们对果蝇中的 MTf 进行了功能分析。与人类同源物类似，果蝇 MTf 是一种脂修饰的、与铁结合的蛋白，附着在上皮细胞膜上，是形成上皮组织中细胞旁通透性屏障的隔膜连接的组成部分。我们证明，上皮成熟过程中的隔膜连接组装依赖于铁结合的 MTf 的内吞作用和顶端侧向再循环。小鼠 MTf 补充了果蝇 MTf 突变体的缺陷。果蝇为 MTf 在上皮连接组装和形态发生中的功能解析提供了第一个遗传模型。
