Mammalian cells secrete a plethora of different proteins such as antibodies, hormones and blood proteins that fulfill their biological function outside the cell. The process of protein secretion starts in the endoplasmic reticulum, a specialized cellular organelle where secretory proteins are synthesized, correctly folded, and sorted into transport vesicles. Efficient packaging of secretory proteins into transport vesicles requires the assistance of so called cargo receptors.
Beat Nyfeler and Hans-Peter Hauri addressed the mechanism of how secretory proteins enter transport vesicles by analyzing the mammalian cargo receptor ERGIC-53. ERGIC-53 is a transmembrane receptor that assists a subset of glycoproteins, including blood coagulation factors V and VIII, in efficient secretion.
To identify novel ERGIC-53 cargo proteins, the scientists developed a genome-wide screening approach based on the complementation of the yellow fluorescent protein (YFP) in living cells. By screening a human liver cDNA library, they identified a1-antitrypsin as previously unrecognized ERGIC-53 cargo protein. a1-antitrypsin is an important liver glycoprotein that is secreted into the blood where it acts as a serine protease inhibitor. Mutations in a1-antitrypsin can cause severe liver and lung diseases in humans.
In their follow up experiments, Nyfeler and Hauri found that the secretion of a1-antitrypsin is significantly delayed in ERGIC-53 knockdown and knockout cells. Interestingly, ERGIC-53 did not bind misfolded mutants of a1-antitrypsin that are known to cause liver and lung diseases in humans. This finding suggests that ERGIC-53 functions in protein quality control, ensuring that only correctly folded a1-antitrypsin is secreted by the liver cells. The novel YFP complementation assay has a promising potential for high-throughput screening of chemicals that can rescue conformational defects of a1-antitrypsin.
In this study Nyfeler and Hauri clearly identified ERGIC-53 as an intracellular cargo receptor of a1-antitrypsin and demonstrated the feasibility of YFP complementation-based cDNA library screening to identify novel protein complexes. Their work is the first successful screening method for the identification of protein complexes in the secretory pathway of living cells on a genome-wide scale.Source article
Alexandra Weber | alfa
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences