Disease relevance of ZRT1

• Using mutant alleles defective for metal-responsive inactivation, we also show that Zrt1 inactivation may be an important mechanism for preventing cadmium uptake and toxicity in zinc-limited cells [1].

High impact information on ZRT1

• While ZRT1 is maximally induced during zinc limitation, ZRT2 is repressed in low zinc but remains induced upon zinc supplementation [2].
• We used a genetic approach to isolate mutants whose ZRT1 expression is no longer repressed in zinc-replete cells, and a new gene, ZAP1, was identified [3].
• To further understand this process at a molecular level, we mapped a region of Zrt1 required for ubiquitination and endocytosis in response to zinc to a domain located on the intracellular surface of the plasma membrane [1].
• During the transition from zinc-limiting to zinc-replete growth conditions (i.e. zinc shock), the Zrt1 transporter is ubiquitinated, endocytosed, and subsequently degraded in the vacuole [1].
• We show here that post-translational inactivation of the yeast Zrt1 zinc uptake transporter is important for zinc homeostasis [1].

Biological context of ZRT1

• Zinc-induced inactivation of the yeast ZRT1 zinc transporter occurs through endocytosis and vacuolar degradation [4].
• These results demonstrate that ubiquitin conjugation is a critical step in the signal transduction pathway that controls the rate of ZRT1 endocytosis in response to zinc [5].
• This domain is a critical cis-acting component of the metal signaling pathway that controls Zrt1 protein trafficking [1].

Anatomical context of ZRT1

• In zinc-limited cells, ZRT1 is a stable, N-glycosylated plasma membrane protein [4].
• Furthermore, immunofluorescence microscopy showed that ZRT1 is localized to the plasma membrane in zinc-limited cells and that the protein is transferred to the vacuole via an endosome-like compartment upon exposure to zinc [4].

Associations of ZRT1 with chemical compounds

• In this work, we verified that yeast cells deleted in ZRT1 were not capable of transporting cadmium, suggesting that the transport of this metal into the cell would be carried out through this zinc transporter [6].
• Finally, mutation of a specific lysine residue in ZRT1 blocks both ubiquitination and endocytosis [5].

Other interactions of ZRT1

• In yeast, zinc uptake is mediated by Zrt1p and Zrt2p, which belong to the ZIP family of metal transporters [7].
• Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter [5].

References