期刊
NATURE CELL BIOLOGY
卷 14, 期 7, 页码 764-774出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2510
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资金
- MitoCheck consortium by European Commission [FP6-503464]
- Federal Ministry of Education and Research (BMBF) in the framework of the National Genome Research Network (NGFN) (NGFN-2 SMP-RNAi) [FKZ01GR0403]
- EU
- Spanish Ministry of Education and Science (MEC)
- Science Foundation Ireland (SFI) [09/IN.1/B2604]
- BMBF NGFN2 SMP-Cell
- Baden Wurttemberg Stiftung, Germany, Programme 'siRNA'
- NGFN-Plus IG-CSG
The secretory pathway in mammalian cells has evolved to facilitate the transfer of cargo molecules to internal and cell surface membranes. Use of automated microscopy-based genome-wide RNA interference screens in cultured human cells allowed us to identify 554 proteins influencing secretion. Cloning, fluorescent-tagging and subcellular localization analysis of 179 of these proteins revealed that more than two-thirds localize to either the cytoplasm or membranes of the secretory and endocytic pathways. The depletion of 143 of them resulted in perturbations in the organization of the COPII and/or COPI vesicular coat complexes of the early secretory pathway, or the morphology of the Golgi complex. Network analyses revealed a so far unappreciated link between early secretory pathway function, small GTP-binding protein regulation, actin cytoskeleton organization and EGF-receptor-mediated signalling. This work provides an important resource for an integrative understanding of global cellular organization and regulation of the secretory pathway in mammalian cells.
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