Biochemists Discover New Biological Mechanism: Transport Factor Divides Protein Synthesis Between Mother And Daughter Cells

‘Learning more about how molecules are asymmetrically distributed during cell division in yeast is important because it can elucidate how other asymmetrical cell divisions might be take place’, says researcher Liesbeth Veenhoff. A division is asymmetrical if the two newly created cells are not identical to each other. Veenhoff: ‘Think, for example, of the differentiation from stem cells to tissue cells. One of the cells differentiates into a specific tissue whereas the other remains a stem cell.’ With yeast, of course, we are not dealing with stem cells. But all cell divisions in yeast are asymmetrical because characteristics of old cells – such as certain types of damage – remain in the mother whereas the daughter starts its life anew.

Two mechanisms known

Proteins can only function properly in the cell if they are in the right location. Previously, two mechanisms for getting proteins to a specific place in the cell were known. In the first, discovered by Nobel Prize winner Günther Blobel, the protein molecules are first synthesized by ribosomes (the molecular machinery for protein synthesis in the cell), which decode the messenger RNA. An address label present on the protein, the equivalent of a zip code, is then recognized by a transport system, which takes the protein to the correct place. In the second known mechanism, the information for the right cellular localization is already read from the particular messenger RNA (mRNA) and the mRNA is transported to the right cellular location, where the proteins are synthesized by ribosomes already present. Characteristic of the newly discovered mechanism is that it does not work for one specific type of protein or mRNA but for a whole set of mRNAs.

Karyopherin-104

Yeast cells multiply in a way that differs from the usual type of cell division, where a cell divides exactly down the middle. In the case of yeast, a daughter cell emerges as a bulge (bud) on the mother cell. The bud then grows out to approximately the size of the mother, for which large amounts of new proteins need to be synthesized. The Groningen biochemists have demonstrated that the protein karyopherin-104 is enriched in the daughter cell. It was already known that karyopherin-104 was responsible for the recycling of the proteins transported with mRNA, en route from the cell nucleus to the ribosome. The new research has revealed that karyopherin-104 not only functions as a transport factor but is also responsible for determining where exactly the protein synthesis takes place.

Surplus of newly synthesized proteins in daughter cell

The localization of karyopherin-104 in the newly forming cell ensures that relatively more mRNA is translated into proteins there. This means that a surplus of proteins can be produced in the daughter cell, thus ensuring that it initially grows faster than the mother cell. The karyopherin-104 is predominantly in the tip of the growing daughter cell at the start of the growing phase and later in the area where the mother and daughter cells touch. Follow-up research should reveal whether the newly discovered mechanism is fundamental to the rejuvenation of daughter cells.

Financial support was provided by the Netherlands Science Foundation NWO (ALW grant number 814.02.002; VENI fellowship to L.M.V.; TopSubsidy to B.P.), the Netherlands Proteomics Centre and the Zernike Institute for Advanced Materials (University of Groningen).