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
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy