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
Warming ponds could accelerate climate change
21.02.2017 | University of Exeter
An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
21.02.2017 | Earth Sciences
21.02.2017 | Medical Engineering
21.02.2017 | Trade Fair News