Authors:
Jeremy C. Simpson, Brigitte Joggerst, Vibor Laketa, Fatima Verissimo, Cihan Cetin, Holger Erfle, Mariana G. Bexiga, Vasanth R. Singan, Jean-Karim Hériché, Beate Neumann, Alvaro Mateos, Jonathon Blake, Stephanie Bechtel, Vladimir Benes, Stefan Wiemann, Jan Ellenberg, & Rainer Pepperkok
Summary:
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.
Source:
Nature Cell Biology; 14, 764-774 (06/03/12)