Rough and Smooth Endoplasmic Reticulum

Definition, Function, Structure and Location

Definition: What is the Endoplasmic Reticulum?

The endoplasmic reticulum (ER) is the largest, membrane-bound intracellular organelle found in eukaryotic cells (prokaryotes lack membrane-bound organelles). It's a highly dynamic organelle that radiates from the nuclear envelope towards the plasma membrane.

Enclosed in the membrane of the endoplasmic reticulum is the lumen that is separate from the cytoplasm (internal environment of the cell apart from the nucleus). However, microscopic studies have shown the lumen to have some connectivity with the nucleus.

Within the cell, the endoplasmic reticulum plays various functions that range from protein synthesis and transport to the metabolism of carbohydrates.


* Depending on the cell, the endoplasmic reticulum may account for as much as 50 percent of the cell volume.

Structure and Location

As already mentioned, the endoplasmic reticulum is the largest or most extended organelle in a majority of eukaryotic cells. While it is made up of a single, continuous membrane system, the endoplasmic reticulum is generally divided into three main parts/morphologies.

These include:


  • Nuclear membrane
  • Tubular network
  • Cisternae

The Nuclear Envelope

The nuclear membrane is composed of two lipid bilayers that make the inner and outer nuclear membrane. Due to the continuity of the endoplasmic reticulum from the nuclear envelope, researchers agree that in eukaryotic organisms, the endoplasmic reticulum was present since development (from prokaryotic/ more primitive cells).

The morphology of the nuclear membrane is maintained by protein linkers. Here, the protein linkers, located in the perinuclear space (NS) maintain a distance of about 50nm between the outer and inner nuclear membrane. As such, protein linkers play an important role in maintaining the morphology of the nuclear membrane/envelope.

Apart from protein linkers, the structure of the nuclear envelope is also enhanced by a number of other molecules. For instance, interactions observed between the proteins of the inner nuclear membrane and chromatin as well as lamin of the outer nuclear membrane and the nuclear pores have been shown to be necessary for the maintenance of the nuclear membrane.

Although the nuclear envelope plays an important role in creating a barrier between the inner part of the nucleus and the cytoplasm (in eukaryotic cells), it consists of hundreds of pores through which various molecules (proteins etc) are transported.

This allows various molecules (e.g. protein molecules) to diffuse out of the nucleus to the cytoplasm where they may be involved in the development/building of different parts of the cell etc.

The rate of diffusion, here, is largely dependent on the molecule size. For instance, whereas molecules that measure up to 9nm in diameter can simple diffuse passively through the nuclear pore complexes, those with a diameter of about 39nm have to be actively transported (in or out of the nucleus).


* The nuclear membrane is composed of nuclear pore complexes.

* The transport system between the nucleus and the cytoplasm is referred to as nucleocytoplasmic transport.

Cisternae (ER Sheets)

Also known as an endoplasmic sheet, the cisternae is the section of the endoplasmic reticulum that makes up part of the peripheral ER.

Under microscopic investigations, the cisternae appear as a series of stacked flat sheets. In cells, they are particularly prominent around the nucleus as they radiate from the nuclear membrane/envelope.

Like the nuclear envelope/nuclear membrane, the endoplasmic sheets are also composed of two lipid bilayers as well as a lumen. The structure of this portion of the endoplasmic reticulum, including the curved regions at the membrane edges, is maintained by several proteins. A good example of this is the CLIMP63, a type II integral membrane protein.

Through interactions achieved between charged coiled-coil domains, the CLIMP63 forms oligomers capable of acting as bridges between the membrane sheets. This, in turn, maintains a specific luminal distance. In the cells of animals, this distance is about 50nm. 

Depletion of this protein has been shown to reduce this distance to about 30nm (luminal distance) proving that it plays a role in maintaining the structure of endoplasmic sheets.


* Sheets of the peripheral ER can vary in size.

* In yeast, the luminal distance is about 30nm.


When ribosomes (and polyribosomes) localize to the sheets of the endoplasmic reticulum, these sheets are referred to as rough sheets, or more commonly, rough endoplasmic reticulum. Here, ribosomes are localized on the cytosolic surface which is the surface between the outer membrane of the endoplasmic reticulum and the cytoplasm.

Localization of these ribosomes to the sheets of the endoplasmic reticulum has been shown to also help regulate their general shape. 


* There are about 1000 ribosomes per square micrometer of the cytosolic face of the endoplasmic reticulum- In total, it is estimated that about 13 million ribosomes are attached to the cytosolic face of the rough ER.


* Part of the endoplasmic reticulum devoid of ribosomes is known as the smooth endoplasmic reticulum (Smooth ER).


* Ribosomes on the endoplasmic reticulum are known as "membrane-bound ribosomes".


On the rough endoplasmic reticulum, ribosomes play an important role in the assembly of proteins. The amount of proteins assembled (through a process known as translation) is largely dependent on the organ/tissue.

For instance, some cells of the digestive system produce high amounts of proteins (enzymes) involved in the digestive process. Proteins may enter the ribosome co-translationally or posttranslationally and ultimately transverse the membrane through the translocon complex.

Endoplasmic Reticulum Tubules 

As compared to the other portions of the endoplasmic reticulum, ER tubules are highly dynamic structures that are continually re-arranging and interconnecting.

They are cylindrical in shape with a diameter that ranges between 30 and 100nm in diameter. Because of the interconnection that takes place at the three-way junctions, ER tubules are loosely packed in what resembles polygonal arrays in the cytoplasm.

With regards to location, ER tubules radiate from both the nuclear membrane and the cisternae. From here, they spread throughout the cytoplasm (to different parts of the cell). As compared to the sheets of the endoplasmic reticulum, ER tubules have a higher membrane curvature as well as surface area to volume ration.

Unlike the rough endoplasmic reticulum, they have fewer ribosomes. As such, they are largely composed of the smooth endoplasmic reticulum.

The shape of tubules is maintained by membrane-associated proteins (e.g. RTNs, DP1) that are also involved in their formation.


* As dynamic structure, ER tubules have been shown to also form and disappear.

* In animals (particularly mammals) ER tubules have been shown to spread throughout the cell. However, they are restricted in close proximity to the cell membrane where they are referred to as cortical ER.


The lumen - is the area of the endoplasmic reticulum that is enclosed by the ER membrane. As such, it's an extensive/elongated area located within the membranes of the ER.

In eukaryotic cells, the lumen is found throughout the cell wherever the ER spreads. Given that the ER radiates from the nuclear membrane, studies have shown the internal compartment of the nucleus to be in continuity with the lumen of the endoplasmic reticulum.


The endoplasmic reticulum is a multi-functional organelle that has the following functions:


Protein Synthesis and Processing

Protein synthesis is one of the major functions of the endoplasmic reticulum. Typically, translation of proteins starts in the cytoplasm. However, some of these proteins are taken to the endoplasmic reticulum (through the translocon) where they undergo folding before being transported to the appropriate destination.

Apart from simply processing proteins, the endoplasmic reticulum is also known as the site for quality control. As such, it ensures that only proteins that are properly processed are transported to the appropriate destination. Here, then, proteins are retained until they attain the right conformation.


* Translation also continues in the ribosome located on the surface of the endoplasmic reticulum (the rough ER).

* Functions of the ER are catalyzed by soluble/membrane-associated proteins.

* From the endoplasmic reticulum, assembled proteins are first transported to the Golgi apparatus from where they can then be transported to other organelles.

Lipid Synthesis

Apart from being the major site for protein synthesis, the endoplasmic reticulum is also the site of lipid biogenesis (biosynthesis of cholesterol and phospholipids). Here, lipid components are first moved to the ER-Golgi intermediate compartment where they are biochemically modified.

Unlike protein synthesis, which mostly occurs in the rough ER, lipid synthesis takes place in the smooth ER which contains enzymes involved in the biosynthetic pathways.

Given that the smooth ER is involved in the biosynthetic pathways of sterol and steroid, it's commonly found in cells of the adrenal gland where a group of steroid hormones are secreted.

Calcium Storage

The endoplasmic reticulum is one of the main storage sites for calcium. Various channels and receptors on the ER membrane are involved in the release of these ions into the cytosol where they help regulate metabolism among other activities.


Aside from various synthetic functions, the endoplasmic reticulum also acts as the transport system for various molecules. For instance, from the cytosol, the endoplasmic reticulum is responsible for the transport of proteins to the Golgi apparatus.

As mentioned, the endoplasmic reticulum spreads from the nuclear membrane to other parts of the cell (towards the plasma membrane). This allows it to transport various molecules from one point to the desired destination. 

Differences between cytosol and cytoplasm

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Amber R. English and Gia K. Voeltz. (2013). Endoplasmic Reticulum Structure and Interconnections with Other Organelles.


Eelco van Anken and Roberto Sitia. (2016). The Endoplasmic Reticulum. ResearchGate. 


Inés Romero-Brey and Ralf Bartenschlager. (2016). Endoplasmic Reticulum: The Favorite Intracellular Niche for Viral Replication and Assembly. 


Junjie Hu, William A. Prinz, and Tom A. Rapopor. (2011). Weaving the Web of ER Tubules.


Schwarz, Dianne S., and Michael D. Blower. (2015). “The endoplasmic reticulum: structure, function and response to cellular signaling.” Cellular and Molecular Life Sciences 



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