The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).


The Endoplasmic Reticulum (ER) organelle is a network of disk-like tubules, sacks and vesicles found in eukaryotic cells. Its main function is to operate as a transport system. Endoplasmic reticulum is chiefly made up of a phospholipid membrane containing an internal fluid-filled space called the cisternal space or the lumen. The ER is folded and stacked layer upon layer within the cell and is connected to the cell's nuclear membrane. Under a microscope, the endoplasmic reticulum is seen as a highly folded structure surrounding the cell nucleus. There are two types of ER, Rough and Smooth.




Structure.
The general structure of the endoplasmic reticulum is an extensive membrane network of cisternae (sac-like structures) held together by the cytoskeleton. The phospholipid membrane encloses a space, the cisternal space (or lumen), from the cytosol. The functions of the endoplasmic reticulum vary greatly depending on the exact type of endoplasmic reticulum and the type of cell in which it resides. The three varieties are called rough endoplasmic reticulum, smooth endoplasmic reticulum and sarcoplasmic reticulum.
The quantity of RER and SER in a cell can quickly interchange from one type to the other, depending on changing metabolic needs: one type will undergo numerous changes including new proteins embedded in the membranes in order to transform. Also, massive changes in the protein content can occur without any noticeable structural changes, depending on the enzymatic needs of the cell


Rough Endoplasmic Reticulum

Rough ER contains ribosomes on its surface, small circular structures that control protein synthesis, making it look bumpy under a microscope. Rough endoplasmic reticulum branches out and expands as protein synthesis increases, providing more surface area for ribosomes to spread out and create more proteins.
During protein synthesis, the ribosomes on the rough ER create new proteins and the ER then folds them properly and sorts them according to function and destination.
The rough ER carries out its protein folding activity deep within the cisternal space. There, newly made proteins are twisted and folded into the configurations necessary for them to carry out their function in the cell.
For sorting, the rough ER works in conjunction with the Golgi apparatus, another cell organelle, to target the newly synthesized proteins to their proper locations. Most proteins produced by ribosomes of the rough endoplasmic reticulum are destined for secretion out of the cell. The RER is key in multiple functions:

• lysosomal enzymes with a mannose-6-phosphate marker added in the cis-Golgi network
• Secreted proteins, either secreted constitutively with no tag, or regulated secretion involving clathrin and paired basic amino acids in the signal peptide.
• integral membrane proteins that stay imbedded in the membrane as vesicles exit and bind to new membranes. Rab proteins are key in targeting the membrane, SNAP and SNARE proteins are key in the fusion event.

Smooth Endoplasmic Reticulum



Smooth ER has a few different functions in the cell, and its functions can vary with cell type. In general, the function of smooth endoplasmic reticulum is to provide surface area for the action of enzymes and to provide storage space for these important enzymes.
In muscle cells, for example, smooth ER stores calcium, releasing it during muscle contraction, triggering the movement of the muscle. In the liver, smooth ER is where detoxification takes place.
Smooth ER also synthesizes lipids (fats) and other components of the cell membrane.
Another function of smooth endoplasmic reticulum is to control the movement of newly synthesized proteins to their proper location in the cell or to the membrane to be sent outside the cell. A process called budding, where small vesicles of smooth ER are pinched off to carry the proteins to their new location, does this.
The many functions of endoplasmic reticulum make it an important organelle for maintaining normal cell functioning. Defective or stressed endoplasmic reticulum has been implicated in diseases ranging from rare genetic conditions to well known conditions such as Alzheimer's disease, diabetes and heart disease. The Smooth ER also contains the enzyme glucose-6-phosphatase which converts glucose-6-phosphate to glucose, a step in gluconeogenesis.





Functions

The endoplasmic reticulum serves many general functions, including the facilitation of protein folding and the transport of synthesized proteins in sacs called cisternae.
Correct folding of newly-made proteins is made possible by several endoplasmic reticulum chaperone proteins, including protein disulfide isomerase (PDI), ERp29, the Hsp70 family member Grp78, calnexin, calreticulin, and the peptidylpropyl isomerase family. Only properly-folded proteins are transported from the rough ER to the Golgi complex.


Transport of proteins


Secretory proteins, mostly glycoproteins, are moved across the endoplasmic reticulum membrane. Proteins that are transported by the endoplasmic reticulum and from there throughout the cell are marked with an address tag called a signal sequence. The N-terminus (one end) of a polypeptide chain (i.e., a protein) contains a few amino acids that work as an address tag, which are removed when the polypeptide reaches its destination. Proteins that are destined for places outside the endoplasmic reticulum are packed into transport vesicles and moved along the cytoskeleton toward their destination.
The endoplasmic reticulum is also part of a protein sorting pathway. It is, in essence, the transportation system of the eukaryotic cell. The majority of endoplasmic reticulum resident proteins are retained in the endoplasmic reticulum through a retention motif. This motif is composed of four amino acids at the end of the protein sequence. The most common retention sequence is KDEL (lys-asp-glu-leu). However, variation on KDEL does occur and other sequences can also give rise to endoplasmic reticulum retention. It is not known if such variation can lead to sub-endoplasmic reticulum localizations. There are three KDEL receptors in mammalian cells, and they have a very high degree of sequence identity. The functional differences between these receptors remain to be established.


Other functions

• Insertion of proteins into the endoplasmic reticulum membrane: Integral membrane proteins are inserted into the endoplasmic reticulum membrane as they are being synthesized (co-translational translocation). Insertion into the endoplasmic reticulum membrane requires the correct topogenic signal sequences in the protein.
• Glycosylation: Glycosylation involves the attachment of oligosaccharides.
• Disulfide bond formation and rearrangement: Disulfide bonds stabilize the tertiary and quaternary structure of many proteins.
• Drug Metabolism: The smooth ER is the site at which some drugs are modified by microsomal enzymes which include the cytochrome P450 enzymes.