10.6084/m9.figshare.4234187.v1
Kuang-Kai Liu
Kuang-Kai
Liu
Wei-Ru Qiu
Wei-Ru
Qiu
Emmanuel Naveen Raj
Emmanuel Naveen
Raj
Huei-Fang Liu
Huei-Fang
Liu
Hou-Syun Huang
Hou-Syun
Huang
Yu-Wei Lin
Yu-Wei
Lin
Chien-Jen Chang
Chien-Jen
Chang
Ting-Hua Chen
Ting-Hua
Chen
Chinpiao Chen
Chinpiao
Chen
Huan-Cheng Chang
Huan-Cheng
Chang
Jenn-Kang Hwang
Jenn-Kang
Hwang
Jui-I Chao
Jui-I
Chao
Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway
Taylor & Francis Group
2016
autophagy receptors
lysosome
nanodiamonds
selective autophagy
ubiquitin
2016-11-15 22:29:28
Dataset
https://tandf.figshare.com/articles/dataset/Ubiquitin-coated_nanodiamonds_bind_to_autophagy_receptors_for_entry_into_the_selective_autophagy_pathway/4234187
<p>Selective macroautophagy/autophagy plays a pivotal role in the processing of foreign pathogens and cellular components to maintain homeostasis in human cells. To date, numerous studies have demonstrated the uptake of nanoparticles by cells, but their intracellular processing through selective autophagy remains unclear. Here we show that carbon-based nanodiamonds (NDs) coated with ubiquitin (Ub) bind to autophagy receptors (SQSTM1 [sequestosome 1], OPTN [optineurin], and CALCOCO2/NDP52 [calcium binding and coiled-coil domain 2]) and are then linked to MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) for entry into the selective autophagy pathway. NDs are ultimately delivered to lysosomes. Ectopically expressed SQSTM1-green fluorescence protein (GFP) could bind to the Ub-coated NDs. By contrast, the Ub-associated domain mutant of SQSTM1 (ΔUBA)-GFP did not bind to the Ub-coated NDs. Chloroquine, an autophagy inhibitor, prevented the ND-containing autophagosomes from fusing with lysosomes. Furthermore, autophagy receptors OPTN and CALCOCO2/NDP52, involved in the processing of bacteria, were found to be involved in the selective autophagy of NDs. However, ND particles located in the lysosomes of cells did not induce mitotic blockage, senescence, or cell death. Single ND clusters in the lysosomes of cells were observed in the xenografted human lung tumors of nude mice. This study demonstrated for the first time that Ub-coated nanoparticles bind to autophagy receptors for entry into the selective autophagy pathway, facilitating their delivery to lysosomes.</p>