The ER, the Golgi, and the secretory pathway

The nuclear envelope is just one piece of a larger network. Many of a eukaryotic cell’s membranes are connected, either directly or by small membrane bubbles that shuttle between them, and together they make, modify, and ship the cell’s products.

The endomembrane system

The endomembrane system is this network of internal membranes plus the plasma membrane. It has seven members:

• nuclear envelope
• endoplasmic reticulum (ER)
• Golgi apparatus
• lysosomes
• vacuoles
• peroxisomes
• plasma membrane

Mitochondria and chloroplasts are not part of the endomembrane system, a favorite exam trap. Materials move between its parts in membrane vesicles, tiny spheres of membrane that bud off one compartment and fuse with another, like shipping containers. The space inside any organelle is its lumen.

The endoplasmic reticulum

The endoplasmic reticulum (ER) (“little net inside the cell”) is a maze of flattened, fluid-filled tubes and sacs called cisternae. Its membrane encloses one continuous space, the ER lumen. The ER comes in two connected forms, rough and smooth, and the rough ER is continuous with the outer membrane of the nuclear envelope.

Rough ER gets its bumpy look from the ribosomes studding its outer surface. It has three jobs:

• starting the sorting of proteins headed for the ER, Golgi, lysosomes, vacuoles, plasma membrane, or the outside of the cell
• inserting newly made proteins into the ER membrane
• glycosylation, attaching carbohydrates (sugar chains) to proteins and lipids

Smooth ER has no ribosomes. Its large membrane surface holds enzymes for four kinds of work:

The Golgi apparatus

The Golgi apparatus is a stack of flattened membrane sacs, each enclosing its own compartment (cisterna). The side facing the ER is the cis Golgi, the side facing the plasma membrane is the trans Golgi, and the sacs between are the medial Golgi. To keep them straight, think of cis as “this side” (next to the ER) and trans as “across” (as in transatlantic).

The Golgi has three overlapping functions:

• Processing. Glycosylation that began in the ER continues here, mostly in the medial Golgi. The Golgi also carries out proteolysis, in which enzymes called proteases cut polypeptides. For example, insulin is made as a larger, inactive precursor, proinsulin, which proteases trim into active insulin just before it is secreted.
• Protein sorting. The Golgi sends proteins on to lysosomes, vacuoles, or the plasma membrane.
• Secretion. It packages cargo into secretory vesicles that fuse with the plasma membrane and release their contents outside the cell.

How cargo gets from one Golgi sac to the next is still debated. There are two models:

The secretory pathway

The route that proteins take to leave the cell is the secretory pathway:

Not everything leaving the Golgi is secreted: it also sends vesicles to other destinations, such as lysosomes.

Palade’s pulse-chase experiment

George Palade traced the secretory pathway with a pulse-chase experiment, using pancreas cells because their main job is secreting proteins. First came the pulse: a brief dose of a radioactive amino acid, so only proteins made during those few minutes were labeled. Then came the chase: a flood of ordinary, nonradioactive amino acid, which stopped any further labeling. Think of painting one batch of cars red and watching where they go on the assembly line.

Electron micrographs taken at later and later times showed the labeled proteins first in the rough ER, then in the Golgi, then in secretory vesicles near the plasma membrane. The conclusion: secreted proteins enter the rough ER as they’re made, then pass through a fixed series of compartments, in order, on their way out.

Check yourselfIn a pulse-chase experiment, why is the chase needed?

The chase floods the cells with unlabeled amino acids so they stop making radioactive proteins. Only the batch made during the pulse is labeled, so its movement from compartment to compartment can be tracked over time.