High impact information on FTR1

• FET3 expression was required for FTR1 protein to be transported to the plasma membrane [1].
• Mutations in a conserved sequence motif of FTR1 specifically blocked iron transport [1].
• Iron-induced degradation of Fet3p-Ftr1p is significantly reduced in strains containing a deletion of a gene, VTA1, which is involved in multivesicular body (MVB) sorting in yeast [2].
• Yeast strains defective in endocytosis (Deltaend4) show a reduced iron-induced loss of Fet3p-Ftr1p [2].
• Strains unable to grow on iron-restricted medium contained deletions of genes that encode the structural components of the high affinity iron transport system (FET3, FTR1), the iron-sensing transcription factor AFT1 or genes required for the assembly of the transport system [3].

Biological context of FTR1

• Suppression of the fet3 fet4 mutant phenotype by FET5 overexpression required the putative FTR1 transporter subunit of the high-affinity system [4].
• The requirement of FTR1 for virulence in a systemic infection model and its role in transferrin iron uptake raise the possibility that transferrin is a source of iron during systemic C. albicans infections [5].
• We examine the (59)Fe uptake kinetics for a number of complexes containing mutant forms of both Fet3p and Ftr1p and demonstrate that a residue in one protein interacts with one in the other protein along the iron trafficking pathway as would be expected in a channeling process [6].

Anatomical context of FTR1

• Ferrous ions are then transported across the plasma membrane through the FET3 oxidase-FTR1 permease complex [7].
• Fet3p-produced Fe(III) is transferred to the permease Ftr1p for import into the cytosol [8].

Associations of FTR1 with chemical compounds

• A mutation of FTR1 did not impair the use of these siderophores but did affect the uptake of ferrioxamines E and B, as well as of ferric citrate, indicating that their utilization was independent of Sit1p [9].
• Fet3, the apparent ferroxidase, is proposed to facilitate iron uptake by catalyzing the oxidation of reductase-generated Fe(II) to Fe(III) by O2; in this model, Fe(III) is the substrate for the iron permease, encoded by FTR1 (Kaplan, J., and O'Halloran, T. V. (1996) Science 271, 1510-1512) [10].
• Fet3p is proposed to facilitate iron uptake by catalyzing the oxidation of Fe(II) to Fe(III) by O2; in this model, Fe(III) is the substrate for the iron permease, encoded by FTR1 [11].
• The high affinity iron uptake complex in the yeast plasma membrane (PM) consists of the ferroxidase, Fet3p, and the ferric iron permease, Ftr1p [12].
• In turn, this might be evidence of a shielding role of the permease Ftr1, which could interact with Fet3 at the level of the aspartate-rich negatively charged region [13].

Physical interactions of FTR1

• Siderophore-iron uptake can occur through the reduction of the complex and the subsequent uptake of iron by the high affinity iron transporter Fet3p/Ftr1p [14].

Other interactions of FTR1

• This Ftr1p mutant supported the plasma membrane targeting of active Fet3p that is blocked in the parental ftr1delta strain [15].
• Here, we characterize the iron transporter homologue Fth1p, which is similar to the high affinity plasma membrane iron transporter Ftr1p [16].
• The high affinity transporters, Ftr1p and Fet3p, are primarily expressed in oxygenated cultures, whereas anaerobic conditions induce the low affinity iron transporter, Fet4p [17].
• Supporting this is that the induction of an Aft1p target gene, FTR1, in response to iron starvation was greatly reduced in pse1-1 cells [18].
• Epitope-tagged Arn1p was expressed in intracellular vesicles in a pattern that was indistinguishable from that of Arn3p, whereas Ftr1p, a component of the high-affinity ferrous system, was expressed on the plasma membrane [19].

Analytical, diagnostic and therapeutic context of FTR1

• The modification of cellular iron metabolism, which involved the increased expression of high-affinity iron transport genes (FET3 and FTR1), was detected via Northern blot analysis [20].

References