| Title | A Novel Size-Based Sorting Mechanism of Pinocytic Luminal Cargoes in Microglia |
| Authors | Chen, Cong Li, Hui-Quan Liu, Yi-jun Guo, Zhi-fei Wu, Hang-jun Li, Xia Lou, Hui-Fang Zhu, Liya Wang, Di Li, Xiao-Ming Yu, Li Cao, Xuetao Lu, Linrong Gao, Zhihua Duan, Shu-Min |
| Affiliation | Zhejiang Univ, Sch Med, Dept Neurobiol,Key Lab Med Neurobiol, Minist Hlth China,Key Lab Neurobiol Zhejiang Prov, Hangzhou 310058, Zhejiang, Peoples R China. Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China. Tsinghua Univ, Sch Life Sci, Tsinghua Univ Peking Univ Joint Ctr Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China. Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China. Zhejiang Sch Med, Key Lab Neurobiol Zhejiang Prov, Key Lab Med Neurobiol, Dept Neurobiol,Minist Hlth China, Hangzhou 310058, Zhejiang, Peoples R China. |
| Keywords | antigen presentation endocytic trafficking luminal contents lysosome microglia size-based sorting TRANS-GOLGI NETWORK COMPLEX CLASS-II ANTIGEN PRESENTATION MACROPINOSOME MATURATION MEDIATED ENDOCYTOSIS LYSOSOME BIOGENESIS DENDRITIC CELLS ATP RELEASE IN-VIVO DYNAMIN |
| Issue Date | 2015 |
| Publisher | journal of neuroscience |
| Citation | JOURNAL OF NEUROSCIENCE.2015,35,(6),2674-2688. |
| Abstract | Microglia are the resident immune cells in the CNS and play diverse roles in the maintenance of CNS homeostasis. Recent studies have shown that microglia continually survey the CNS microenvironment and scavenge cell debris and aberrant proteins by phagocytosis and pinocytosis, and that reactive microglia are capable to present antigens to T cells and initiate immune responses. However, how microglia process the endocytosed contents and evoke an immune response remain unclear. Here we report that a size-dependent selective transport of small soluble contents from the pinosomal lumen into lysosomes is critical for the antigen processing in microglia. Using fluorescent probes and water-soluble magnetic nanobeads of defined sizes, we showed in cultured rodent microglia, and in a cell-free reconstructed system that pinocytosed proteins become degraded immediately following pinocytosis and the resulting peptides are selectively delivered to major histocompatibility complex class II (MHC-II) containing lysosomes, whereas undegraded proteins are retained in the pinosomal lumen. This early size-based sorting of pinosomal contents relied on the formation of transient tunnel between pinosomes and lysosomes in a Rab7- and dynamin II-dependent manner, which allowed the small contents to pass through but restricted large ones. Inhibition of the size-based sorting markedly reduced proliferation and cytokine release of cocultured CD4(+) T cells, indicating that the size-based sorting is required for efficient antigen presentation by microglial cells. Together, these findings reveal a novel early sorting mechanism for pinosomal luminal contents in microglial cells, which may explain how microglia efficiently process protein antigens and evoke an immune response. |
| URI | http://hdl.handle.net/20.500.11897/341485 |
| ISSN | 0270-6474 |
| DOI | 10.1523/JNEUROSCI.4389-14.2015 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生命科学学院 |
