Title : An iron-regulated and glycosylation-dependent proteasomal degradation pathway for the plasma membrane metal transporter
ZIP14
Abstract :
- Protein degradation is instrumental in regulating cellular function
- Plasma membrane proteins targeted for degradation are internalized and sorted to multivesicular bodies, which fuse with lysosomes, where they are degraded
- ZIP14 is a newly identified iron transporter with multitransmembrane domains
- In an attempt to dissect the molecular mechanisms by which iron regulates ZIP14 levels, we found that ZIP14 is endocytosed, extracted from membranes, deglycosylated, and degraded by proteasomes
- This pathway did not depend on the retrograde trafficking to the endoplasmic reticulum and thus did not involve the well-defined endoplasmic reticulum-associated protein degradation pathway
- Iron inhibited membrane extraction of internalized ZIP14 , resulting in higher steady-state levels of ZIP14
- Asparagine-linked (N-linked) glycosylation of ZIP14 , particularly the glycosylation at N102 , was required for efficient membrane extraction of ZIP14 and therefore is necessary for its iron sensitivity
- These findings highlight the importance of proteasomes in the degradation of endocytosed plasma membrane proteins