Scientists map the entire active protein inventory in cells

Working with colleagues from Denmark, Canada, China, and the U.S.A., the scientists have shown how cutting-edge methods can be used to catalogue the entire inventory of active proteins in cell organelles at a particular moment. Their work sheds considerable light on how cells use proteins.

The work is published in the journal Cell.

Cells are like small cities. They contain all the necessary parts that allow their infrastructure, function, growth, and communication to operate. For over a century scientists have been looking at the structures and organelles in cells using microscopic methods, and then drawing conclusions about their function. Biochemical methods have allowed scientists to examine the inner life of the cell, an organisational unit basic to all life. Now, they are clarifying its structures in detail: from mitochondria, the "factories" of cells, which create energy; to the endoplasmic reticulum, necessary for protein synthesis and metabolic processes; to the Golgi apparatus, responsible for lipid synthesis and producing important energy reserves for cell growth.

Now scientists led by Matthias Mann have specialised in identifying individual proteins in protein complexes. Proteins have various functions in a cell, from transport to mechanical support. As enzymes, they catalyse all kinds of metabolic processes. They are also important components of signal chains, like those which transmit information from the exterior of the cell to its nucleus. In this way, proteins also control the transcription of genetic information and the synthesis of new proteins that comes with it.

In this study, the proteome researchers looked at liver cells in mice. Using mass spectrometry, and by comparing databases, the scientists were able to detect more than 1400 proteins, localised in ten different cell compartments. Previous analyses had shown that certain proteins assign themselves clearly to particular cell organelles. When the scientists took the protein complex apart, these proteins were used as markers. Proteins which appear together with these marker-proteins could now also be assigned their proper place in the inventory. This method, called protein correlation profiling, was developed by Matthias Mann and his colleagues, and has previously been successfully used to determine the composition of single cell-organelle protein.

After the individual "compartments" for the proteins were identified, the scientists compared corresponding protein sets of individual cell organelles. Among the 1400 different proteins that can be clearly mapped onto individual cell organs, around 40% of them also appear in other cell organs. This result can be compared with studies on yeast cells. Their proteins have stayed "true" to their cell organelles over the course of evolution. Their localisation has apparently remained stable over almost a billion years, as simple organisms evolved all the way to mammals.

These results are a milestone in cell biology. Matthias Mann says, "for the first time, we are able to determine where exactly in the cell large numbers of proteins belong. It allows a new understanding of their function and interaction with other cellular proteins and cell organelles." The researchers hope that protein correlation profiling will allow them to determine which proteins participate in failures of regulation. This could contribute to research into diseases which occur when communication between cells is disturbed.