A research group led by Prof. Xiaohua Huang from the School of Chemistry and Materials Science of Nanjing Normal University, in collaboration with Prof. Xingwang Deng at Peking University, Zhenbiao Yang at the University of California, Riverside and other researchers, has identified an unconventional mechanism for extracellular cargoes, specifically rare earth elements (REEs), that arabinogalactan proteins (AGPs) act as extracellular cargo receptors and move across the plasma membrane to initiate endocytosis. This significant achievement has been published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), entitled “Arabinogalactan protein-rare earth element complexes activate plant endocytosis”.
Endocytosis is essential to all eukaryotes, but how cargoes are selected for internalization remains poorly characterized. Extracellular cargoes are thought to be selected by transmembrane receptors that bind intracellular adaptors proteins to initiate endocytosis. In their research, Prof. Huang and her research team visualized the dynamics of an extracellular cargo receptor protein by using stimulated emission depletion microscopy and found a mechanism for clathrin-mediated endocytosis (CME) of extracellular lanthanum [La(III)] cargoes, which requires extracellular arabinogalactan proteins (AGPs) that are anchored on the outer face of the plasma membrane. AGPs were colocalized with La(III) on the cell surface and in La(III)-induced endocytic vesicles in Arabidopsis leaf cells. Super-resolution imaging showed that La(III) triggered AGP movement across the plasma membrane. AGPs were then colocalized and physically associated with the μ subunit of the intracellular adaptor protein 2 (AP2) complexes. The AGP-AP2 interaction was independent of CME, whereas AGP’s internalization required CME and AP2. Moreover, we show that AGP-dependent endocytosis in the presence of La(III) also occurred in human cells.
These findings indicate that extracellular AGPs act as conserved CME cargo receptors, REEs promote the cross-membrane translocation of its extracellular cargo receptor AGPs to activate their endocytosis, thus challenging the current paradigm about endocytosis of extracellular cargoes and also providing insight into the mechanism for the activation of CME, the biological role of AGPs, and the cellular mechanisms of REE actions in plants.
This work was financially supported by the National Natural Science Foundation of China (Grant No.21371100, 21501068 and 31170477).