Smooth Endoplasmic Reticulum Definition

The smooth endoplasmic reticulum (smooth ER) is a membranous organelle found in most eukaryotic cells. It is a subset of the endomembrane system of the endoplasmic reticulum. Its main functions are the synthesis of lipids, steroid hormones, the detoxification of harmful metabolic byproducts and the storage and metabolism of calcium ions within the cell. The smooth ER is distinguished from the other parts of the endoplasmic reticulum by the absence of membrane-bound ribosomes. This organelle is also morphologically distinct, often made of tubular structures called cisternae.

Smooth ER is prominent in cells of the liver that process harmful chemicals, in cells of the endocrine system such as those in the adrenals that produce steroid hormones, and in excitable cells such as neurons and muscle cells that use Ca2+ signaling.

Structure of the Smooth Endoplasmic Reticulum

The smooth endoplasmic reticulum is primarily composed of three-dimensional polygonal networks of tubules called cisternae. They are about 50 nm in diameter in mammals and 30 nm in diameter in yeast. The high curvature of these structures needs to be stabilized by many proteins, including reticulons, DP1 and receptor expression enhancing proteins (REEPs). These proteins either bend the membrane through structural elements that wedge themselves into the lipid bilayer or shape the membrane through oligomerization. The presence of these proteins seems crucial for the existence of tubular cisternae since their suppression or deletion leads to an excess of flattened sac-like structures in the ER and a near complete absence of tubules.

The smooth ER is also a dynamic structure, with new tubules budding off from the sides of existing structures. With the aid of GTP hydrolysis, some tubule branches can also fuse with one another. The extent of the smooth ER network depends on the actin and microtubule cytoskeleton of the cell. ER tubules can slide along the cytoskeletal framework using motor proteins, or grow along with a microtubule at its plus end.

The structure of the smooth ER is of particular significance in two types of cells in the human body – muscle cells and neurons. The presence of an extensive ER network along the neuron is closely associated with its interaction with actin and microtubules and the organelle forms a continuous network across the entire cell. It is present in small dendritic spines, all along the narrow axon, and is spread across the synapse. At the synapse, the smooth ER is often associated with mitochondria. Even when the cytoskeleton depolymerizes, and the ER network of tubules undergoes major morphological changes, the association between mitochondria and smooth ER remains intact. In muscle cells, the smooth endoplasmic reticulum is called the sarcoplasmic reticulum and is an important locus for the storage of calcium ions.

Skeletal muscle

Image shows a skeletal muscle, with the sarcoplasmic reticulum colored blue. Along with special structures in the plasma membrane of the muscle cell (T-tubules), the sarcoplasmic reticulum plays an important role in the contraction of muscle fibers.

Functions of the Smooth Endoplasmic Reticulum

The smooth ER is important in the synthesis of lipids, such as cholesterol and phospholipids, which form all the membranes of the organism. In addition it is important for the synthesis and secretion of steroid hormones from cholesterol and other lipid precursors. In addition, it is involved in carbohydrate metabolism. For instance, the final reaction of gluconeogenesis occurs in the lumen of the smooth ER since it contains the enzyme glucose-6-phosphatase. This enzyme catalyzes the production of glucose from glucose-6-phosphate.

The dynamic nature of the smooth endoplasmic reticulum is particularly important in the liver that detoxifies a number of substances and makes them easy to remove from the body. For instance, when there is a sudden and drastic increase in the amount of some lipid soluble drugs in the body, the smooth ER of hepatocytes in the liver metabolize them into water-soluble compounds, so that they can be excreted in the urine. In order to do this, the smooth ER network of a hepatocyte can nearly double in size and then revert to its original shape and size after the chemical assault has been neutralized.

Lipid Synthesis

Steroid-secreting cells are characterized by abundant smooth endoplasmic reticulum whose membranes contain the enzymes involved in sterol and steroid synthesis.

The adrenal cortex is an important organ for the synthesis and secretion of steroid hormones. Cells involved in this process contain an extensive ER network. While there is a wide range of hormones produced by the cells of the adrenal glands, they can be classified broadly as glucocorticoids, mineralocorticoids, and sex hormones. Sex hormones are produced in much larger quantities in the gonads, but glucocorticoids and mineralocorticoids are produced largely in the adrenal glands and are synthesized from cholesterol. Cholesterol is converted into a number of different steroid molecules, with the reactions being catalyzed by the enzymes of the cytochrome p450 family of proteins. Some parts of this pathway reside in the ER and others occur in mitochondria.

There has been some evidence to suggest that cells that are heavily involved in lipid metabolism contain relatively little rough endoplasmic reticulum, in spite of the obvious need for a variety of enzymes. In such cells, researchers have identified smooth ER subfractions that contain proteins normally seen in the rough endoplasmic reticulum, such as the translocon complex and chaperone proteins. This suggests that the smooth ER can also be involved in protein synthesis, cotranslational import of polypeptides and quality control for newly synthesized proteins.

Calcium Store

The role of the smooth endoplasmic reticulum in calcium ion storage and release is of particular importance in the cells of the nervous and muscular system that use calcium-mediated signaling for excitation and contraction. Under resting conditions, the ER lumen can be partially full. After a great influx of calcium into the cell during excitation, the smooth endoplasmic reticulum can act as a sink, allowing the cells to recover from the effects of membrane depolarization. The ER can store and release calcium ions in complex ways, and in some scenarios, can even be implicated in creating a ‘memory’ of neuronal activity.

The presence of two types of transmembrane Ca2+ channels on the ER membrane allow this sophisticated signaling process. These are inositol-1,4,5-trisphosphate receptors (InsP3Rs)and ryanodine receptors (RYRs). Some Ca2+-ion mediated ATPase enzymes also direct the interaction of ER Ca2+ stores with the plasma membrane and mitochondria. The extensive smooth ER network within neurons modulates the excitation and transmission of nerve impulses from one cell to another, and even allows local changes to Ca2+ concentration.

The smooth endoplasmic reticulum of muscle cells is even more extensively modified. While every muscle fiber needs the coordinated release of Ca2+ from the sarcoplasmic reticulum in order to contract as a single unit, this property becomes even more important in cardiac muscle cells. Synchronous activation of over 10,000 Ca2+ spark events results in the entire cell being transiently bathed in Ca2+ ions. This activates cardiac myofilaments and results in their contraction. After the contraction event, the smooth ER functions as a sink for these ions, allowing the cells to quickly return to their relaxed state.

There is also increasing evidence that the interaction between the ER and mitochondria is not only important for lipid metabolism but also for coordinating the signals from the cell and inducing apoptosis. In many models of programmed cell death, Ca2+ ion release from the ER is necessary for the activation of apoptotic proteins. Some proteins within the ER are also effector enzymes in this pathway. Evidence is emerging that the ER can even induce apoptosis through Ca2+ signaling when the cell is under stress.

  • Ca2+ spark – Intracellular Ca2+ release events important for the coordination between excitation and contraction of a cell. Particularly important in muscle cells.
  • Endosymbionts – Organisms that live within other organisms. Mitochondria are considered ancient endosymbionts of early eukaryotic cells.
  • Motor Proteins – Proteins that function as molecular motors, converting chemical energy to mechanical energy, while moving along a suitable surface.
  • Rough Endoplasmic Reticulum – Sections of the ER membrane containing membrane-bound ribosomes.


1. Which of these is true about the smooth endoplasmic reticulum?
A. Dependent on the intermediate filaments of the cytoskeleton
B. Made of tubular cisternae that are 100 nm in diameter
C. Interaction with mitochondria influences a number of its functions
D. All of the above

Answer to Question #1
C is correct. The interaction of smooth ER with mitochondria not only influences its functions in carbohydrate and lipid metabolism but also plays an important role in integrating the signals of the entire cell and inducing apoptosis under certain conditions. While the formation of the endoplasmic reticulum is dependent on the cytoskeletal machinery of the cell, particularly microtubules, the importance of intermediate filaments is not very clear. The ER is made of tubular cisternae and two-dimensional sheets. However, the diameter of cisternae rarely exceeds 60 nm. In yeast, they are even smaller, with a diameter of about 30 nm.

2. Which of these is a function of smooth endoplasmic reticulum?
A. Synthesis and secretion of steroid hormones
B. Maintenance and regeneration of the plasma membrane
C. Storage and release of Ca2+ ions
D. All of the above

Answer to Question #2
D is correct. The SER forms a three-dimensional polygonal network across the cell and is often made of cisternae. It contains a number of enzymes involved in sterol and steroid hormone synthesis. Its role in the creation of cholesterol and phospholipid makes it important in the generation and maintenance of the plasma membrane and the entire endomembrane system. It also stores and releases calcium – a function that is particularly important in excitable cells.

3. Which of these proteins influence the calcium store of smooth ER?
A. Receptor expression enhancing proteins (REEPs)
B. Ryanodine receptors and Inositol-1,4,5-trisphosphate receptors
C. Reticulons and DP1
D. All of the above

Answer to Question #3
B is correct. REEPs, reticulons and DP1 are involved in stabilizing the curved structure of ER tubules. However, it is ryanodine receptors and inositol-1,4,5-trisphophate receptors that influence its calcium store.