The endoplasmic reticulum (ER) is an organelle of cells in eukaryotic organisms that forms an interconnected network of membrane vesicles. According to the structure the endoplasmic reticulum is classified into two types, that is, rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER). The rough endoplasmic reticulum is studded with ribosomes on the cytosolic face. These are the sites of protein synthesis. The rough endoplasmic reticulum is predominantly found in hepatocytes where protein synthesis occurs actively. The smooth endoplasmic reticulum is a smooth network without the ribosomes. The smooth endoplasmic reticulum is concerned with lipid metabolism, carbohydrate metabolism and detoxification. The smooth endoplasmic reticulum is abundantly found in mammalian liver and gonad cells. The lacey membranes of the endoplasmic reticulum were first seen by Keith R. Porter, Albert Claude, and Ernest F. Fullam in the year 1945.
The general structure of the endoplasmic reticulum is a membranous network of cisternae (sac-like structures) held together by the cytoskeleton. The phospholipid membrane encloses a space, the cisternal space (or lumen), which is continuous with the perinuclear space but separate from the cytosol. The functions of the endoplasmic reticulum vary greatly depending on its cell type, cell function, and cell needs. The ER can even modify to change over time in response to cell needs. The three most common varieties are called rough endoplasmic reticulum, smooth endoplasmic reticulum, and sarcoplasmic reticulum.
The quantity of RER and SER in a cell can slowly interchange from one type to the other, depending on changing metabolic needs. Transformation can include embedment of new proteins in membrane as well as structural changes. Massive changes may also occur in protein content without noticeable structural changes.
Rough endoplasmic reticulum 
The surface of the rough endoplasmic reticulum (often abbreviated RER) is studded with protein-manufacturing ribosomes giving it a "rough" appearance (hence its name). The binding site of the ribosome on the rough endoplasmic reticulum is the translocon. However, the ribosomes bound to it at any one time are not a stable part of this organelle's structure as they are constantly being bound and released from the membrane. A ribosome binds to the endoplasmic reticulum only when it begins to synthesize a protein destined for the secretory pathway. There, a ribosome in the cytosol begins synthesizing a protein until a signal recognition particle recognizes the signal peptide of 5–30 hydrophobic amino acids, sometimes preceded by a positively charged amino acid. This signal sequence allows the recognition particle to bind to the ribosome, causing the ribosome to bind to the rough endoplasmic reticulum and pass the new protein through the rough endoplasmic reticulum membrane. The signal peptide is then cleaved off within the lumen of the ER by a signal peptidase. Ribosomes at this point may be released back into the cytosol, however non-translating ribosomes are also known to stay associated with translocons.
The membrane of the rough endoplasmic reticulum forms large double membrane sheets that are located near, and continuous with the outer layer of the nuclear envelope. Although there is no continuous membrane between the endoplasmic reticulum and the Golgi apparatus, membrane-bound vesicles shuttle proteins between these two compartments. Vesicles are surrounded by coating proteins called COPI and COPII. COPII targets vesicles to the golgi apparatus and COPI marks them to be brought back to the rough endoplasmic reticulum. The rough endoplasmic reticulum works in concert with the golgi complex to target new proteins to their proper destinations. A second method of transport out of the endoplasmic reticulum involves areas called membrane contact sites, where the membranes of the endoplasmic reticulum and other organelles are held closely together, allowing the transfer of lipids and other small molecules.
The rough endoplasmic reticulum is key in multiple functions:
- Manufacture of lysosomal enzymes with a mannose-6-phosphate marker added in the cis-Golgi network
- Manufacture of secreted proteins, either secreted constitutively with no tag or secreted in a regulatory manner involving clathrin and paired basic amino acids in the signal peptide.
- Integral membrane proteins that stay embedded 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.
- Initial glycosylation as assembly continues. This is N-linked (O-linking occurs in the golgi).
Endoplasmic reticulum stress 
Disturbances in redox regulation, calcium regulation, glucose deprivation, and viral infection can lead to endoplasmic reticulum stress. It is a state in which the folding of proteins slows leading to an increase in unfolded proteins. This stress is emerging as a potential cause of damage in hypoxia/ischemia, insulin resistance and other disorders.
Smooth endoplasmic reticulum 
The smooth endoplasmic reticulum (abbreviated SER) has functions in several metabolic processes. It synthesizes lipids, phospholipids and steroids—cells which secrete these products, such as those in the testes, ovaries, and skin oil glands have a great deal of smooth endoplasmic reticulum. It also carries out the metabolism of carbohydrates, drug detoxification, attachment of receptors on cell membrane proteins, and steroid metabolism. In muscle cells, it regulates calcium ion concentration. It is connected to the nuclear envelope. Smooth endoplasmic reticulum is found in a variety of cell types (both animal and plant), and it serves different functions in each. The smooth endoplasmic reticulum also contains the enzyme glucose-6-phosphatase, which converts glucose-6-phosphate to glucose, a step in gluconeogenesis. It consists of tubules that are located near the cell periphery. These tubes sometimes branch forming a network that is reticular in appearance. In some cells, there are dilated areas like the sacs of rough endoplasmic reticulum. The network of smooth endoplasmic reticulum allows increased surface area for the action or storage of key enzymes and the products of these enzymes.
Sarcoplasmic reticulum 
The sarcoplasmic reticulum (SR), from the Greek sarx, ("flesh"), is smooth ER found in smooth and striated muscle. The only structural difference between this organelle and the smooth endoplasmic reticulum is the medley of proteins they have, both bound to their membranes and drifting within the confines of their lumens. This fundamental difference is indicative of their functions: The endoplasmic reticulum synthesizes molecules, while the sarcoplasmic reticulum stores and pumps calcium ions. The sarcoplasmic reticulum contains large stores of calcium, which it sequesters and then releases when the muscle cell is stimulated. It plays a major role in excitation-contraction coupling.
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 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 its resident proteins are retained within it 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 whether such variation can lead to sub-ER 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.
See also 
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- Shibata, Yoko; Voeltz, Gia K.; Rapoport, Tom A. (2006). "Rough Sheets and Smooth Tubules". Cell 126 (3): 435–439. doi:10.1016/j.cell.2006.07.019. ISSN 00928674.
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- Levine T (September 2004). "Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions". Trends Cell Biol. 14 (9): 483–90. doi:10.1016/j.tcb.2004.07.017. PMID 15350976.
- Levine T, Loewen C (August 2006). "Inter-organelle membrane contact sites: through a glass, darkly". Curr. Opin. Cell Biol. 18 (4): 371–8. doi:10.1016/j.ceb.2006.06.011. PMID 16806880.
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- [Functions of Smooth ER "Functions of Smooth ER"] Check
|url=scheme (help). University of Minnesota Duluth. Retrieved 16 December 2012.
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- Toyoshima C, Nakasako M, Nomura H, Ogawa H (2000). "Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution". Nature 405 (6787): 647–55. doi:10.1038/35015017. PMID 10864315.
- Medical Cell Biology 3rd/ed. Academic Press. p. 69.
|Wikimedia Commons has media related to: Endoplasmic reticulum|
- Lipid and protein composition of Endoplasmic reticulum in OPM database
- Animations of the various cell functions referenced here