PAIRing Up Cargo Proteins 英文参考文献.docVIP

Synopsis PAIRingUpCargoProteins CharlesQ.Choi* FreelanceScienceWriter,NewYork,NewYork,UnitedStatesofAmerica Allnewlymadeproteinsdestinedtobe secreted from our cells or to function at the cell surface—and many of those that function in membranes within the cell— start their lives in a convoluted heap of membranes within cells called the endo- plasmic reticulum (ER). From there, they begin a journey that will take them through the stacked membrane compart- ments of the Golgi apparatus to their eventual destinations, transported from one compartment to another in small membrane vesicles. Proteins known as cargo receptors often perform the key function of selecting and tethering cargo proteins within the transport vesicles, but only a few such receptors have been identified to date, and which cargo proteins they pair with was mostly un- known. Now, Maya Schuldiner and her colleagues have devised a large-scale approach to discover these pairings be- tweencargoproteinsandcargoreceptors, laying the groundwork to uncover the mechanisms that underlie this indispens- ablemachinery. Towards a cellular ‘‘Traffickome.’’ Systematic analysis of cargo receptors (CRs) demonstratestherulesgoverningspecificityversuspromiscuityinERexit. doi:10.1371/journal.pbio.1001334.g001 Thescientistscalltheirapproach‘‘pair- ing analysis of cargo receptors’’, or PAIRS. They start with yeast strains that have mutations incandidate cargorecep- tors—proteinsthatpreviousstudiesfound were involved in traffic between the ER andtheGolgiapparatus.Aroboticsystem then systematically crosses these mutant yeast strains with a collection of other strains,eachofwhichcontainsapotential cargo protein tagged with green fluores- cent protein (GFP). The researchers then useanautomatedhigh-throughputmicro- scope to help see which of the resulting strainshaveretainedgreenfluorescencein theERduetothecargoproteinaccumu- lating in the absence of its functional receptor. This strategy can be used to uncoverthe