Journal of Clinical & Experimental Pharmacology

Abstract

The Non-classical Pathway is the Major Pathway to Secrete Proteins in Saccharomyces cerevisiae

Kathryn R Stein, Bennett J Giardina and Hui-Ling Chiang

Protein secretion is a fundamental process in all living cells. Proteins that contain the ER signal are secreted by the classical pathway, whereas proteins without the ER sequence are secreted via the non-classical pathway. Recent evidence indicates that a large number of signal-less proteins including metabolic enzymes, transcriptional factors, translation factors, heat shock proteins, and anti-oxidant proteins are secreted by a variety of cells that range from bacteria to human. Furthermore, the secretion of gluconeogenic enzymes has been observed in bacteria, fungi, parasites, and mammalian cells. Gluconeogenic enzymes are secreted into the periplasm when Saccharomyces cerevisiae are grown in low glucose. The distribution of gluconeogenic enzymes in the periplasm/ extracellular fraction of Saccharomyces cerevisiae was observed by immuno-TEM, confirmed with an extraction protocol, and identified in a large-scale proteomic study. It is expected that there are other proteins that lack the ER signal sequence and utilize the non-classical pathway to be secreted. Indeed, 92 proteins were identified that were present in the extracellular fraction using proteomics and more than 95% of the proteins do not have the ER sequence. Thus, the non-classical pathway is the major pathway to secrete proteins in Saccharomyces cerevisiae. This review article focuses on the use of multiple techniques including immuno-TEM, an extraction protocol, and proteomics to identify proteins that are present in the extracellular fraction in Saccharomyces cerevisiae, and to compare the dataset produced in yeast with other secretomic studies performed on a range of organisms from bacteria to human cells. Common proteins include metabolic enzymes, heat shock proteins, anti-oxidant proteins, and translation factors. Therefore, the secretion of these proteins is widely observed across species.