Protein Synthesis and Secretion: Animal Cells

Abstract

Many products of interest to the biotechnology industry are synthesized and secreted from specialized cell types. Among the most significant products are those having therapeutic application such as hormones, plasma proteins, and enzymes produced by the endocrine and exocrine glands (for a survey on biopharmaceuticals see Walsh G. Biopharmaceutical products in the US and European markets. 6th ed. BioPlan Associates, Inc.; 2007). The production of many bioproducts takes advantage of recombinant DNA technology to construct vectors designed for high‐level expression and secretion of proteins. Remarkably, a variety of cultured mammalian cells have the capacity to synthesize and secrete a vast array of biologically active proteins that are normally produced only in highly specialized cells. Despite the higher cost of production compared to bacteria, yeast, or insect cells, protein expression in mammalian cells is often obligatory to produce proteins in an enzymatic or biologically active form. However, the particular requirements protein may have often limits the yield and reduces the quality of proteins produced in mammalian cells. To understand factors that affect the quality of proteins, it is necessary to consider what factors affect protein folding, processing, and secretion from mammalian cells. Remarkable progress has been made during the past two decades in understanding the molecular basis of protein secretion. This article briefly describes how proteins are synthesized, processed, and transported through the secretory pathway to the cell surface. Particular emphasis is focused on the early secretory pathway because this is frequently the rate‐limiting step. Biotechnology can take advantage of our expanding knowledge of the secretory pathway to design new strategies to improve and optimize the secretion of high‐quality recombinant proteins from mammalian cells.