Endoplasmic Reticulum (ER): Structure, Types, and Functions

The endoplasmic reticulum, or ER, is the cell's manufacturing and transport network. It is a vast, folded system of membranes that runs through the cytoplasm, and it comes in two forms that do two different jobs: the rough ER builds and folds proteins, and the smooth ER makes lipids and detoxifies.

Understanding the ER as a two-part production line, and how it hands its products on to the Golgi for shipping, is the foundation for understanding how a cell makes almost everything it needs.

What is the endoplasmic reticulum?

The endoplasmic reticulum is an extensive network of membrane-enclosed tubes and flattened sacs that fills much of the cytoplasm of eukaryotic cells. The space enclosed inside these membranes is called the lumen (or cisternal space).

The ER is directly continuous with the outer membrane of the nuclear envelope, so its interior is connected to the space around the nucleus. In some cells the ER can occupy up to half the total membrane of the cell. It is one of the largest organelles, and it is found in essentially all eukaryotic cells, though a few, such as mature red blood cells, lack it. Prokaryotes (bacteria) have no endoplasmic reticulum.

The ER exists in two forms, rough and smooth, distinguished by whether ribosomes are attached to its surface.

Discovery of the endoplasmic reticulum

The ER was first clearly seen using the electron microscope by Keith Porter, Albert Claude, and Ernest Fullam in 1945, who described a "lace-like reticulum" in cultured cells. Porter coined the name "endoplasmic reticulum" in 1953 ("reticulum" means little network).

Two earlier and related names are still used and often asked about. In 1897, Garnier described the basophilic, ribosome-rich regions of certain cells under the light microscope and called them the ergastoplasm, which we now recognize as the rough ER. And in 1902, Emilio Veratti described a fine network in muscle cells, the sarcoplasmic reticulum, now understood to be the specialized smooth ER of muscle.

Structure of the endoplasmic reticulum

The ER is built from three kinds of membrane structure.

Cisternae

The cisternae are long, flattened, sac-like membranes arranged in parallel stacks. Their surfaces are often studded with ribosomes, so cisternae are typical of the rough ER, and are prominent in cells that secrete a lot of protein. (The membrane itself is very thin, only about 5 to 6 nm across, thinner than the plasma membrane.)

Vesicles

The vesicles are small, rounded, membrane-bound sacs. They bud from the ER to carry materials, and are especially abundant in the smooth ER and in active secretory cells such as those of the pancreas.

Tubules

The tubules are smooth-walled, branching tubes that form an interconnected network. They are characteristic of the smooth ER and are common in non-secretory cells such as muscle cells. They take part in membrane transport and in linking parts of the ER network together.

Types of endoplasmic reticulum

The single most important idea about the ER is the division of labor between its two forms.

Rough endoplasmic reticulum (RER)

The rough ER is called "rough" because ribosomes are attached to its outer (cytoplasmic) surface, giving it a studded, granular appearance. The ribosomes are bound through membrane proteins called ribophorins. The rough ER is mostly made of flattened cisternae and is prominent near the nucleus.

Its main job is making and processing proteins. Ribosomes on the RER synthesize proteins that are destined for secretion, for the plasma membrane, or for other organelles. As these proteins are made, they are threaded into the ER lumen, folded, and given early modifications such as the start of glycosylation (adding sugar chains). The RER is abundant in cells that make a lot of protein, such as pancreatic cells, plasma cells (which secrete antibodies), and liver cells. Because of its ribosomes and RNA, the RER stains strongly with basic dyes (it is basophilic), which is why the older name for it is ergastoplasm.

Smooth endoplasmic reticulum (SER)

The smooth ER has no ribosomes, so its membrane looks smooth. It is mostly tubular. It is also called the agranular ER. Its jobs are quite different from the RER:

• Lipid and steroid synthesis: the SER makes phospholipids, cholesterol, and steroid hormones. It is abundant in hormone-producing cells such as those of the testes, ovaries, and adrenal glands.
• Detoxification: in liver cells, the SER contains enzymes that break down drugs, alcohol, and other harmful substances into safer forms the body can excrete.
• Carbohydrate and glycogen metabolism: the SER takes part in releasing glucose from stored glycogen.
• Calcium storage: in muscle cells, a specialized SER called the sarcoplasmic reticulum stores calcium ions and releases them to trigger muscle contraction.

Rough vs smooth ER: a comparison

Location of the endoplasmic reticulum

The ER is found throughout the cytoplasm of almost all eukaryotic cells, both animal and plant. It is continuous with the nuclear envelope and spreads out from there as a network reaching much of the cell. The rough ER tends to lie closer to the nucleus, and the smooth ER extends further toward the plasma membrane. Mature red blood cells, which lose most organelles as they develop, do not have an ER.

The ER and the secretory pathway

It helps to see the ER as the first stage of the cell's production and shipping line. A protein bound for secretion is made by ribosomes on the rough ER and folded in the ER lumen. It is then packaged into a vesicle that carries it to the Golgi apparatus, where it is further modified, sorted, and shipped to its final destination. This ER-to-Golgi-to-destination route is called the secretory pathway, and the ER is where it begins.

Functions of the endoplasmic reticulum (summary)

• Protein synthesis and folding (rough ER).
• Lipid, cholesterol, and steroid hormone synthesis (smooth ER).
• Detoxification of drugs and poisons (smooth ER, especially in the liver).
• Calcium storage and release for muscle contraction (sarcoplasmic reticulum).
• Transport of proteins and lipids, handing them on to the Golgi.
• Membrane production, making new membrane material for the cell.
• Carbohydrate metabolism, including releasing glucose from glycogen.

How to Remember

Rough makes protein, smooth makes lipid. Rough ER has ribosomes (protein factories), so it makes protein. Smooth ER has none, and handles lipids, steroids, and detox. Ribosomes equal protein; no ribosomes equals lipids.

Rough is near the nucleus, smooth reaches outward. The rough ER sits close to the nucleus (where the mRNA comes from); the smooth ER extends toward the cell membrane. Rough is close, smooth is far.

Ergastoplasm equals rough ER. The old name for the ribosome-rich, deeply staining rough ER is ergastoplasm. If a question uses "ergastoplasm," it means rough ER.

Sarcoplasmic reticulum is muscle's smooth ER. In muscle cells, the smooth ER is specialized to store calcium for contraction, and is called the sarcoplasmic reticulum.

ER then Golgi: make it, then ship it. The ER makes and folds proteins and lipids; the Golgi finishes and ships them. The ER is stage one of the production line.

Key exam facts

Where Students Get Confused

Smooth ER has ribosomes too, just fewer. No. Smooth ER has no ribosomes at all; that is what makes it smooth. Rough ER has ribosomes; smooth ER does not.

The ER makes proteins by itself. The ribosomes on the rough ER make the proteins; the ER provides the space to fold and modify them. Smooth ER, having no ribosomes, does not make protein at all.

The ER is continuous with the Golgi and the plasma membrane. The ER is directly continuous only with the nuclear envelope. It connects to the Golgi by sending vesicles, not by a continuous membrane, and it is not continuous with the plasma membrane.

Ergastoplasm and sarcoplasmic reticulum are the same thing. They are different. Ergastoplasm is another name for rough ER. Sarcoplasmic reticulum is the specialized smooth ER of muscle cells.

Rough and smooth ER are separate organelles. They are two regions of one continuous membrane system. One can transition into the other, and both are part of the same endoplasmic reticulum.

References

1. Alberts B, Heald R, Johnson A, et al. Molecular Biology of the Cell. 7th ed. New York: W. W. Norton; 2022.
2. Iwasa J, Marshall W. Karp's Cell and Molecular Biology. 8th ed. Hoboken: Wiley; 2016.
3. Reece JB, Urry LA, Cain ML, et al. Campbell Biology. 12th ed. New York: Pearson; 2021.