与铁转运蛋白突变相关的铁过载的分子和临床关联
Molecular and clinical correlates in iron overload associated with mutations in ferroportin.
作者信息
De Domenico Ivana, McVey Ward Diane, Nemeth Elizabeta, Ganz Tomas, Corradini Elena, Ferrara Francesca, Musci Giovanni, Pietrangelo Antonello, Kaplan Jerry
机构信息
Dipartimento di Scienze Microbiologiche Genetiche e Molecolari, Università di Messina, 98166 Messina, Italia.
出版信息
Haematologica. 2006 Aug;91(8):1092-5.
Abstract
Mutations in ferroportin (Fpn) result in iron overload. We correlate the behavior of three Fpn mutants in vitro with patients' phenotypes. Patients with Fpn mutations A77D or N174I showed macrophage iron loading. In cultured cells, FpnA77D did not reach the cell surface and cells did not export iron. Fpn mutant N174I showed plasma membrane and intracellular localization, and did not transport iron. Fpn mutation G80S was targeted to the cell surface and was transport competent, however patients showed macrophage iron. We suggest that FpnG80S represents a class of Fpn mutants whose behavior in vitro does not explain the patients' phenotype.
摘要
铁转运蛋白（Fpn）突变会导致铁过载。我们将三种Fpn突变体在体外的行为与患者的表型进行关联。携带Fpn突变A77D或N174I的患者表现出巨噬细胞铁负荷增加。在培养细胞中，FpnA77D未到达细胞表面，细胞也不输出铁。Fpn突变体N174I表现出质膜和细胞内定位，且不转运铁。Fpn突变G80S定位于细胞表面且具有转运能力，然而患者却表现出巨噬细胞铁负荷增加。我们认为FpnG80S代表了一类Fpn突变体，其在体外的行为无法解释患者的表型。
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