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Proteins: Exit This Way

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Cells secrete numerous proteins, but these proteins do not exit the cell surface from just anywhere, according to a study conducted jointly by two Institut Curie Research Center teams and published in the Journal of Cell Biology.

Stéphanie Miserey-Lenkei is a member of Bruno Goud’s Molecular Mechanisms of Intracellular Transport team and is interested in the role of the protein RAB6. RAB6 is found in the Golgi apparatus and regulates the protein secretion process within cells. Protein secretion is essential to the life of both cells and organisms. Proteins secreted by a given cell act as messengers in long-distance communication with other cells. They can also remain on the cell surface and provide anchoring points with the cell environment or points for interaction with other cells within the tissue.

Gaelle Boncompain, a member of Franck Perez’s Dynamics of Intracellular Organization team, which focuses on intracellular transport mechanisms, has developed tools to not only synchronize protein secretion (the RUSH system) but to block proteins at the point at which they leave the cell (the SPI system). These tools are now used by numerous other laboratories worldwide.

Working with their postgraduate students, the two researchers combined their expertise to show how secreted proteins follow very specific pathways within vesicles that guide them—as though on rails—from the Golgi apparatus to preferential secretion sites on the cell surface. Furthermore, they found that these sites are located exactly at the points at which cells attach to their environment. “We also observed that, regardless of the type of protein secreted, it is always the transport system involving RAB6 that is used. And the molecular motors involved and the microtubules, the “rails”, are the same,” explains Stéphanie Miserey-Lenkei.

In cancer, many studies have found that secreted proteins are transported abnormally. Cell surface proteins are involved in the migration and adhesion of cells within their environment. “It will be important to figure out the role played by the forces exerted by and on the cell, as well as to test the existence of these preferential secretion sites in three-dimensional cultures,” points out Gaelle Boncompain. The researchers still need to work out why these preferential secretion sites exist. They already have several hypotheses and their upcoming work should be able to tell us more. 

RAB6 and Microtubules Restrict Protein Secretion to Focal Adhesions

Lou Fourriere, Amal Kasri, Nelly Gareil, Sabine Bardin, Hugo Bousquet, David Pereira, Franck Perez, Bruno Goud, Gaelle Boncompain, Stéphanie Miserey-Lenkei

The Journal of Cell Biology May 2019, jcb.201805002; DOI: 10.1083/jcb.201805002