College of Life Science, Capital Normal University, Beijing, China.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Traffic. 2018 Feb;19(2):122-137. doi: 10.1111/tra.12540. Epub 2017 Dec 5.
Iron is essential for most living organisms. The iron-regulated transporter1 (IRT1) plays a major role in iron uptake in roots, and its trafficking from endoplasmic reticulum (ER) to plasma membrane (PM) is tightly coordinated with changes in iron environment. However, studies on the IRT1 response are limited. Here, we report that Malus xiaojinesis IRT1 (MxIRT1) associates with detergent-resistant membranes (DRMs, a biochemical counterpart of PM microdomains), whereas the PM microdomains are known platforms for signal transduction in the PM. Depending on the shift of MxIRT1 from microdomains to homogeneous regions in PM, MxIRT1-mediated iron absorption is activated by the cholesterol recognition/interaction amino acid consensus (CRAC) motif of MxIRT1. MxIRT1 initially associates with DRMs in ER via its transmembrane domain 1 (TMD1), and thus begins DRMs-dependent intracellular trafficking. Subsequently, MxIRT1 is sequestered in COPII vesicles via the ER export signal sequence in MxIRT1. These studies suggest that iron homeostasis is influenced by the CRAC motif and TMD1 domain due to their determination of MxIRT1-DRMs association.
铁是大多数生物必需的元素。铁调节转运蛋白 1（IRT1）在根中摄取铁方面起着重要作用，其从内质网（ER）到质膜（PM）的运输与铁环境的变化密切协调。然而，IRT1 响应的研究有限。在这里，我们报告说，苹果属矮生系 IRT1（MxIRT1）与去污剂抗性膜（DRMs，质膜微域的生化对应物）相关联，而质膜微域是质膜中信号转导的已知平台。根据 MxIRT1 从小域到质膜均匀区域的转移，MxIRT1 介导的铁吸收被 MxIRT1 的胆固醇识别/相互作用氨基酸共识（CRAC）基序激活。MxIRT1 最初通过其跨膜结构域 1（TMD1）与 ER 中的 DRMs 相关联，从而开始依赖 DRMs 的细胞内运输。随后，MxIRT1 通过 MxIRT1 中的 ER 输出信号序列被 COPII 囊泡隔离。这些研究表明，由于 CRAC 基序和 TMD1 结构域决定了 MxIRT1-DRMs 的关联，因此铁稳态受到 CRAC 基序和 TMD1 结构域的影响。
