Yang, Zinger (2017) The Retromer Complex Member VPS35 regulates Iron Homeostasis through mediating Hepcidin-induced Ferroportin Degradation. Harvard University's Electronic Thesis and Dissertation .

Abstract

The Hepcidin mediated degradation of iron exporter Ferroportin is an essential mechanism for iron homeostasis. Upon Hepcidin binding, Ferroportin is rapidly internalized and degraded. However, the underlying mechanism for the degradation has not been uncovered. Using a functional genomics approach, VPS35, a member of the retromer complex, is identified as an important mediator for Hepcidin-induced Ferroportin degradation. Cells with CRISPR induced mutation in VPS35 demonstrated significantly reduced Ferroportin degradation in the presence of Hepcidin. Interestingly, VPS35 mutations and dysfunction of other members of the retromer complex have been associated with familial autosomal-dominant Parkinson’s disease, a progressive neurodegenerative diseases with well established iron accumulation phenotype. The result of this study reveal a previously unappreciated role for retromer in the regulation of iron homeostasis.

Item Type:	Article
Date Deposited:	26 Sep 2017 00:45
Last Modified:	26 Sep 2017 00:45
URI:	https://oak.novartis.com/id/eprint/33689