| Title | Oligopeptide transporter Slc15A modulates macropinocytosis in Dictyostelium by maintaining intracellular nutrient status |
| Authors | Zhang, Yiwei Tu, Hui Hao, Yazhou Li, Dong Yang, Yihong Yuan, Ye Guo, Zhonglong Li, Lei Wang, Haibin Cai, Huaqing |
| Affiliation | Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China Univ Sci & Technol China, Div Life Sci & Med, Hefei 230027, Peoples R China Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China Peking Univ, Sch Adv Agr Sci, Beijing 100871, Peoples R China |
| Keywords | MACROPINOSOME FORMATION RAS PHAGOCYTOSIS PROTEIN PHOSPHOINOSITIDES |
| Issue Date | Apr-2022 |
| Publisher | JOURNAL OF CELL SCIENCE |
| Abstract | Macropinocytosis mediates non-selective bulk uptake of extracellular fluid. It is the major route by which axenic Dictyostelium cells obtain nutrients and has emerged as a nutrient-scavenging pathway in mammalian cells. How environmental and cellular nutrient status modulates macropinocytic activity is not well understood. By developing a high-content imaging-based genetic screen in Dictyostelium discoideum we identified Slc15A, an oligopeptide transporter located at the plasma membrane and early macropinosome, as a novel macropinocytosis regulator. We show that deletion of slc15A but not two other related slc15genes, leads to reduced macropinocytosis, reduced cell growth and aberrantly increased autophagy in cells grown in nutrient-rich medium. Expression of Slc15A protein or supplying cells with free amino acids rescues these defects. In contrast, expression of transport-defective Slc15A or supplying cells with amino acids in their di-peptide forms fails to rescue these defects. Therefore, Slc15A modulates the level of macropinocytosis by maintaining the intracellular availability of key amino acids through extraction of oligopeptides from the early macropinocytic pathway. We propose that Slc15A constitutes part of a positive feedback mechanism coupling cellular nutrient status and macropinocytosis. This article has an associated First Person interview with the first authors of the paper. |
| URI | http://hdl.handle.net/20.500.11897/642375 |
| ISSN | 0021-9533 |
| DOI | 10.1242/jcs.259450 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 现代农学院 |
