All eukaryotic cells have an endoplasmic reticulum (ER). The ER is a convoluted organelle, made up of tubules and flattened sacs, whose membrane is continuous with the membrane of the nucleus. The ER usually has a very large surface area, and its membrane is where cellular lipids are synthesized (see Chapter 7). The ER is also where most membrane proteins are assembled, including those of the plasma membrane and the membranes of the lysosomes, ER, and Golgi complex. In addition, all soluble proteins that will eventually be secreted from the cell—as well as those destined for the lumen of the ER, Golgi complex, or lysosomes—are initially delivered to the ER lumen (see Figure 13-1). Since the ER plays such an important role in protein secretion, we refer to the pathway of protein trafficking that flows through the ER as the secretory pathway. For simplicity, we will refer to all proteins initially targeted to the ER as secretory proteins, but keep in mind that not all proteins that are targeted to the ER are actually secreted from the cell.

In this first section of the chapter, we discuss how proteins are initially identified as secretory proteins and how such proteins are translocated across the ER membrane. We deal first with soluble proteins—those that pass all the way through the ER membrane, into the lumen. In the next section, we discuss integral membrane proteins, which are inserted into the ER membrane.

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