The Secrets of Secretion


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Prof. Jeffrey Gerst, Michael Marash: fundamental life mechanism


Let's talk about secretion. This suggestion would probably cause more than a few raised eyebrows - especially if offered by the media. But science writing has its fair share of unusual tasks, which mirror the incredible diversity of scientific research. Take for instance the efforts to better understand secretion processes in yeast, the current research focus of Prof. Jeffrey Gerst and doctoral student Michael Marash of the Weizmann Institute's Molecular Genetics Department.
As it turns out, the study of yeast and other less-developed organisms holds the key to a better understanding of human cell secretion. In fact, the obvious differences between yeast, flies, and people dwindle unexpectedly when their mechanisms of secretion are closely observed.
Secretion, one of the most fundamental mechanisms of life, plays a central role in communication among living cells and is also involved in their construction and growth. Because the genes controlling this mechanism are well conserved in evolution, variations among species are relatively slight.
Gerst studies the genetic factors responsible for the cellular secretion of such substances as hormones and neurotransmitters. The secretion process begins with the formation, inside the cell, of a bubble containing the substance to be secreted. This bubble, or "vesicle," consists of a membrane of fatty molecules called phospholipids (the same molecules as those forming the cell membrane). When the secretion process is set in motion, it causes the vesicle to fuse with the cell membrane, resulting in the vesicle's contents spilling into the intercellular space (the space between cells). Vesicle-cell fusion is also an essential stage of cell growth: when the vesicle fuses with the membrane, the cell's surface grows, just as a quilt would expand if new patches were incorporated into its fabric.
How exactly does fusion between the vesicle and the cell membrane take place? Gerst, together with two other groups, found that this process is regulated by three proteins: Snc, Sso, and Sec9. Apparently, Sso and Sec9 are "irreplaceable" - when damaged, the secretion process is arrested and the cell dies. But more recently, Gerst has revealed that the third protein, Snc, has a "backup system." When this protein is damaged, genetic mutations in two other proteins (Vbm 1 and 2) may occur to restore cell growth and secretion. These mutations also have an interesting side effect - they lead to the cell's accumulation of precursors, called ceramides, required to build certain lipids.
The research team has now simulated this backup mechanism, leading to an important discovery - a "master switch" regulating secretion. When the scientists added ceramide precursors directly to the cells, the secreting cells continued to live and secrete properly even though one of the fusion factors was missing. The introduced material is, in effect, a sort of a chemical trigger that activates an enzyme, called a phosphatase, which breaks off a phosphorus-containing group of molecules from various proteins. The scientists established that this trigger operates not only in the backup system but also in Sso, one of the two "irreplaceable" fusion proteins.
Thus by identifying the "backup system" of one of the fusion proteins, Gerst and his team discovered the master switch. When one of the "irreplaceable" fusion proteins contains phosphorus, secretion is prevented; but when the phosphatase enzyme is activated and removes the phosphorus, the protein initiates membrane fusion, which in turn leads to secretion. The newly discovered role of this phospatase in secretion also shed s light on the enzyme's vital function in the growth of living cells.
A better understanding of these processes may lead to future ways of controlling the secretion process of various cells. For example, it may be possible to regulate the secretion of neurotransmitters by nerve cells, which could help treat degenerative brain diseases, or to control the secretion of hormones and other signaling chemicals, resulting in advanced cancer-treatments.