Research of the iron-regulated transporter 1 (IRT1) in the past decades and its latest development

Abstract

Iron (Fe) is an essential element in organisms and plays a critical role in important biochemical processes. As a result, Fe deficiency limits plant growth and development and seriously affects human health. However, developing strategies to improve Fe content is challenging because Fe is also toxic at higher levels. In plants, IRT1, a ZIP family member, is the main Fe transporter. Therefore, there is an urgent need to study IRT1 to understand the mechanism of Fe absorption. Recent research has focused on three aspects: Firstly, investigation of the role of transcription factors in regulating IRT1 in response to Fe condition have identified. FER-like iron deficiency induced transcription factor (FIT), a basic helix-loop-helix (bHLH) protein, as the central transcriptional regulator of Fe uptake. Apparently, the FIT protein can form heterodimers with bHLH038, bHLH039, bHLH100, or bHLH101 in order to upregulate Fe-uptake genes, including IRT1 , that affect Fe homeostasisvia plant hormone signaling pathway. Secondly, recent studies have also investigated the modification of IRT1 proteins in regulating the intracellular traffic of IRT1. These studies have shown that IRT1 accumulates at the trans-Golgi network and then travels to the plasma membrane. For example, the monoubiquitination of lysine residues (K154 and K179) induces IRT1 to undergo clathrin-mediated endocytosis from the plasma membrane; IRT1 degradation factor 1 (IDF1) functions as a E3 ubiquitin ligase for the ubiquitination of IRT1; and the endosomal proteins SORTING NEXIN1 (SNX1) and FYVE1 (FYVE domain-containing protein) participate in recycling IRT1 to the plasma membrane. Thirdly, recent studies have investigated the use of IRT1 application in biofortification. Indeed, many IRT1s have been transformed into rice and have been shown to improve the micro-nutrition of the grain. Based on these studies, we first discussed the multi-transmembrane structure and important sites in metal transport. The signal peptide in the N-terminus of IRT1 directs the protein to the endoplasmic reticulum and initiates protein synthesis and trafficking. Key sites in the loop between transmembrane domains III and IV, such as lysines and histidines, are crucial for maintaining Fe homeostasis. The regulation network of IRT1 at the transcript level is also summarized. Briefly, gibberellin, ethylene, and nitric oxide regulate the expression of Fe-utilization genes by affecting FIT activity, whereas the COP9 signalosome subunit 6 (CSN6) is down-regulated during early stages of Fe deficiency, which ensures the rapid accumulation of IDEF1, and in turn, up-regulates Fe uptake- and utilization-related genes that help reduce the stress of Fe deficiency in rice. In contrast, BTS, an E3 ubiquitin ligase, negatively regulates Fe absorption by regulating the stability of downstream factors. In addition, we analyzed the intracellular trafficking of IRT1 at the subcellular level. Accordingly, we also present the route of intracellular IRT1 trafficking and describe the factors that affect IRT1 recycling between the plasma membrane and trans-Golgi network. Finally, we describe the persisting challenges with a focus on the additional unknown roles of the transmembrane domain in intracellular trafficking and of the membrane raft in Fe homeostasis, and propose future research directions. We hope this review provides insight into the regulation of Fe uptake by plants.