| First Author | Wang X | Year | 2021 |
| Journal | J Biol Chem | Pages | 100426 |
| PubMed ID | 33609526 | Mgi Jnum | J:304807 |
| Mgi Id | MGI:6512664 | Doi | 10.1016/j.jbc.2021.100426 |
| Citation | Wang X, et al. (2021) FLCN regulates transferrin receptor 1 transport and iron homeostasis. J Biol Chem :100426 |
| abstractText | Birt-Hogg-Dube (BHD) syndrome is a multiorgan disorder caused by inactivation of the folliculin (FLCN) protein. Previously, we identified FLCN as a binding protein of Rab11A, a key regulator of the endocytic recycling pathway. This finding implies that the abnormal localization of specific proteins whose transport requires the FLCN-Rab11A complex may contribute to BHD. Here, we used human kidney-derived HEK293 cells as a model, and we report that FLCN promotes the binding of Rab11A with transferrin receptor 1 (TfR1), which is required for iron uptake through continuous trafficking between the cell surface and the cytoplasm. Loss of FLCN attenuated the Rab11A-TfR1 interaction, resulting in delayed recycling transport of TfR1. This delay caused an iron deficiency condition that induced hypoxia-inducible factor (HIF) activity, which was reversed by iron supplementation. In a Drosophila model of BHD syndrome, we further demonstrated that the phenotype of BHD mutant larvae was substantially rescued by an iron-rich diet. These findings reveal a conserved function of FLCN in iron metabolism and may help to elucidate the mechanisms driving BHD syndrome. |
