Editing Endoplasmic reticulum (section)

== Structure ==
[[File:Nucleus ER golgi.svg|thumb|300px|'''1'''&nbsp;[[Cell nucleus|Nucleus]]{{nbsp|2}}
'''2'''&nbsp;[[Nuclear pore]]{{nbsp|2}}
'''3'''&nbsp;Rough endoplasmic reticulum (RER){{nbsp|2}}
'''4'''&nbsp;Smooth endoplasmic reticulum (SER){{nbsp|2}}
'''5'''&nbsp;[[Ribosome]] on the rough ER{{nbsp|2}}
'''6'''&nbsp;[[Protein]]s that are transported{{nbsp|2}}
'''7'''&nbsp;Transport [[Vesicle (biology)|vesicle]]{{nbsp|2}}
'''8'''&nbsp;[[Golgi apparatus]]{{nbsp|2}}
'''9'''&nbsp;Cis face of the Golgi apparatus{{nbsp|2}}
'''10'''&nbsp;Trans face of the Golgi apparatus{{nbsp|2}}
'''11'''&nbsp;Cisternae of the Golgi apparatus]]

The general structure of the endoplasmic reticulum is a network of membranes called [[cisterna]]e. These sac-like structures are held together by the [[cytoskeleton]]. The [[phospholipid membrane]] encloses the cisternal space (or lumen), which is continuous with the [[perinuclear space]] but separate from the [[cytosol]]. The functions of the endoplasmic reticulum can be summarized as the synthesis and export of proteins and membrane lipids, but varies between ER and cell type and cell function.  The quantity of both rough and smooth endoplasmic reticulum in a cell can slowly interchange from one type to the other, depending on the changing metabolic activities of the cell.  Transformation can include embedding of new proteins in membrane as well as structural changes.  Changes in protein content may occur without noticeable structural changes.<ref name="Alberts-2002">{{cite book | last1 = Alberts | first1 = Bruce | last2 = Johnson | first2 = Alexander | last3 = Lewis | first3 = Julian | last4 = Raff | first4 = Martin | last5 = Roberts | first5 = Keith | last6 = Walter | first6 = Peter | name-list-style = vanc | title = Molecular biology of the cell | date = 2002 | publisher = Garland Science | location = New York | isbn = 978-0-8153-3218-3 | edition = 4th | url = https://www.ncbi.nlm.nih.gov/books/NBK26841/ | url-status = live | archive-url = https://web.archive.org/web/20171003052046/https://www.ncbi.nlm.nih.gov/books/NBK26841/ | archive-date = 2017-10-03 }}</ref><ref>{{cite book|last1=Cooper|first1=Geoffrey M.|name-list-style=vanc|title=The cell: a molecular approach|date=2000|publisher=ASM Press|location=Washington (DC)|isbn=978-0-87893-106-4|edition=2nd|url=https://archive.org/details/cell00geof|url-access=registration}}</ref>

===Rough endoplasmic reticulum===
[[File: Protein translation.gif|thumb|300px|A 2-minute animation showing how a protein destined for the [[secretory pathway]] is synthesized and secreted into the rough endoplasmic reticulum, which appears at the upper right approximately halfway through the animation]]
The surface of the rough endoplasmic reticulum (often abbreviated ''RER'' or ''rough ER''; also called ''granular endoplasmic reticulum'') is studded with protein-manufacturing [[ribosome]]s giving it a "rough" appearance (hence its name).<ref>{{cite web|title=reticulum|url=http://medical-dictionary.thefreedictionary.com/reticulum|website=The Free Dictionary}}</ref> The binding site of the ribosome on the rough endoplasmic reticulum is the [[translocon]].<ref>{{cite journal | vauthors = Görlich D, Prehn S, Hartmann E, Kalies KU, Rapoport TA | title = A mammalian homolog of SEC61p and SECYp is associated with ribosomes and nascent polypeptides during translocation | journal = Cell | volume = 71 | issue = 3 | pages = 489–503 | date = October 1992 | pmid = 1423609 | doi = 10.1016/0092-8674(92)90517-G | s2cid = 19078317 }}</ref> However, the ribosomes are not a stable part of this organelle's structure as they are constantly being bound and released from the membrane. A ribosome only binds to the RER once a specific protein-nucleic acid complex forms in the cytosol.  This special complex forms when a free ribosome begins [[translation (biology)|translating]] the [[mRNA]] of a protein destined for the [[secretory pathway]].<ref name="Lodish-2003">{{cite book |last=Lodish |first=Harvey |name-list-style=vanc |year=2003 |title=Molecular Cell Biology |edition=5th |publisher=W. H. Freeman |pages=[https://archive.org/details/molecularcellbio00harv/page/659 659–666] |isbn=978-0-7167-4366-8 |display-authors=etal |url-access=registration |url=https://archive.org/details/molecularcellbio00harv/page/659 }}</ref> The first 5–30 [[amino acid]]s polymerized encode a [[signal peptide]], a molecular message that is recognized and bound by a [[signal recognition particle]] (SRP). Translation pauses and the ribosome complex binds to the RER [[translocon]] where translation continues with the [[ribosome-nascent chain complex|nascent]] (new) protein forming into the RER lumen and/or membrane. The protein is processed in the ER lumen by an enzyme (a signal [[peptidase]]), which removes the signal peptide. Ribosomes at this point may be released back into the cytosol; however, non-translating ribosomes are also known to stay associated with translocons.<ref name="Seiser-2000">{{cite journal | vauthors = Seiser RM, Nicchitta CV | title = The fate of membrane-bound ribosomes following the termination of protein synthesis | journal = The Journal of Biological Chemistry | volume = 275 | issue = 43 | pages = 33820–7 | date = October 2000 | pmid = 10931837 | doi = 10.1074/jbc.M004462200 | doi-access = free }}</ref>

The membrane of the rough endoplasmic reticulum is in the form of large double-membrane sheets that are located near, and continuous with, the outer layer of the [[nuclear envelope]].<ref name="Shibata-2006">{{cite journal | vauthors = Shibata Y, Voeltz GK, Rapoport TA | title = Rough sheets and smooth tubules | journal = Cell | volume = 126 | issue = 3 | pages = 435–9 | date = August 2006 | pmid = 16901774 | doi = 10.1016/j.cell.2006.07.019 | s2cid = 16107069 | doi-access = free }}</ref> The double membrane sheets are stacked and connected through several right- or left-handed helical ramps, the "Terasaki ramps", giving rise to a structure resembling  a [[parking garage]].<ref name="Terasaki-2013">{{cite journal | vauthors = Terasaki M, Shemesh T, Kasthuri N, Klemm RW, Schalek R, Hayworth KJ, Hand AR, Yankova M, Huber G, Lichtman JW, Rapoport TA, Kozlov MM | title = Stacked endoplasmic reticulum sheets are connected by helicoidal membrane motifs | journal = Cell | volume = 154 | issue = 2 | pages = 285–96 | date = July 2013 | pmid = 23870120 | pmc = 3767119 | doi = 10.1016/j.cell.2013.06.031 }}</ref><ref name="Guven-2014">{{cite journal | vauthors = Guven J, Huber G, Valencia DM | title = Terasaki spiral ramps in the rough endoplasmic reticulum | journal = Physical Review Letters | volume = 113 | issue = 18 | pages = 188101 | date = October 2014 | pmid = 25396396 | doi = 10.1103/PhysRevLett.113.188101 | bibcode = 2014PhRvL.113r8101G }}</ref> Although there is no continuous membrane between the endoplasmic reticulum and the [[Golgi apparatus]], membrane-bound [[Vesicle (biology and chemistry)#Transport vesicle|transport vesicles]] shuttle proteins between these two compartments.<ref>Endoplasmic reticulum. (n.d.). [[McGraw-Hill Encyclopedia of Science and Technology]]. Retrieved September 13, 2006, from Answers.com Web site: {{cite web |url=http://www.answers.com/topic/endoplasmic-reticulum |title=Answers - the Most Trusted Place for Answering Life's Questions |website=[[Answers.com]] |access-date=2006-09-13 |url-status=live |archive-url=https://web.archive.org/web/20061116131259/http://www.answers.com/topic/endoplasmic-reticulum |archive-date=2006-11-16 }}</ref> Vesicles are surrounded by [[Vesicular transport adaptor protein|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 [[protein targeting|target new proteins]] to their proper destinations. The second method of transport out of the endoplasmic reticulum involves areas called [[membrane contact site]]s, where the membranes of the endoplasmic reticulum and other organelles are held closely together, allowing the transfer of lipids and other small molecules.<ref>{{cite journal | vauthors = Levine T | title = Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions | journal = Trends in Cell Biology | volume = 14 | issue = 9 | pages = 483–90 | date = September 2004 | pmid = 15350976 | doi = 10.1016/j.tcb.2004.07.017 }}</ref><ref>{{cite journal | vauthors = Levine T, Loewen C | title = Inter-organelle membrane contact sites: through a glass, darkly | journal = Current Opinion in Cell Biology | volume = 18 | issue = 4 | pages = 371–8 | date = August 2006 | pmid = 16806880 | doi = 10.1016/j.ceb.2006.06.011 }}</ref>

The rough endoplasmic reticulum is key in multiple functions:
* Manufacture of [[Lysosome|lysosomal]] enzymes with a [[mannose-6-phosphate]] marker added in the ''cis''-Golgi network.<ref>{{Cite journal |last1=Čaval |first1=Tomislav |last2=Zhu |first2=Jing |last3=Tian |first3=Weihua |last4=Remmelzwaal |first4=Sanne |last5=Yang |first5=Zhang |last6=Clausen |first6=Henrik |last7=Heck |first7=Albert J. R. |date=2019-01-01 |title=Targeted Analysis of Lysosomal Directed Proteins and Their Sites of Mannose-6-phosphate Modification*[S] |journal=Molecular & Cellular Proteomics |volume=18 |issue=1 |pages=16–27 |doi=10.1074/mcp.RA118.000967 |doi-access=free |pmid=30237200 |issn=1535-9476|pmc=6317476 }}</ref>
* Manufacture of [[Secretion|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 (G-protein)|Rab]] proteins are key in targeting the membrane; [[SNAP-25|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).
** N-linked glycosylation: If the protein is properly folded, [[oligosaccharyltransferase]] recognizes the AA sequence [[Asparagine|N]]X[[serine|S]] or [[Asparagine|N]]X[[threonine|T]] (with the S/T residue phosphorylated) and adds a 14-sugar backbone (2-''N''-acetylglucosamine, 9-branching [[mannose]], and 3-[[glucose]] at the end) to the side-chain [[nitrogen]] of Asn.

The RER has ribosomes while the SER does not.

===Smooth endoplasmic reticulum===
[[File:0313 Endoplasmic Reticulum c labeled.png|thumb|left|250px|Electron micrograph showing smooth ER (arrow) in mouse tissue, at 110,510× magnification]]

In most cells the smooth endoplasmic reticulum (abbreviated '''SER''') is scarce. Instead there are areas where the ER is partly smooth and partly rough, this area is called the transitional ER. The transitional ER gets its name because it contains ER exit sites. These are areas where the transport vesicles which contain lipids and proteins made in the ER, detach from the ER and start moving to the [[Golgi apparatus]]. Specialized cells can have a lot of smooth endoplasmic reticulum and in these cells the smooth ER has many functions.<ref name="Alberts-2002" /> It synthesizes [[lipids]], [[phospholipids]],<ref>{{cite journal |last1=Kannan |first1=Muthukumar |last2=Lahiri |first2=Sujoy |last3=Liu |first3=Li-Ka |last4=Choudhary |first4=Vineet |last5=Prinz |first5=William A. |title=Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER |journal=Journal of Lipid Research |date=March 2017 |volume=58 |issue=3 |pages=553–562 |doi=10.1194/jlr.M072959  |doi-access=free |pmid=28119445 |pmc=5335585 }}</ref><ref>{{cite journal |last1=Kannan |first1=Muthukumar |last2=Riekhof |first2=Wayne R. |last3=Voelker |first3=Dennis R. |title=Transport of Phosphatidylserine from the Endoplasmic Reticulum to the Site of Phosphatidylserine Decarboxylase2 in Yeast: Phosphatidylserine Transport to the Locus of Psd2p |journal=Traffic |date=February 2015 |volume=16 |issue=2 |pages=123–134 |doi=10.1111/tra.12236 |pmid=25355612 |s2cid=34302 |doi-access= }}</ref><ref>{{cite journal |last1=Friedman |first1=Jonathan R. |last2=Kannan |first2=Muthukumar |last3=Toulmay |first3=Alexandre |last4=Jan |first4=Calvin H. |last5=Weissman |first5=Jonathan S. |last6=Prinz |first6=William A. |last7=Nunnari |first7=Jodi |title=Lipid Homeostasis Is Maintained by Dual Targeting of the Mitochondrial PE Biosynthesis Enzyme to the ER |journal=Developmental Cell |date=January 2018 |volume=44 |issue=2 |pages=261–270.e6 |doi=10.1016/j.devcel.2017.11.023 |pmid=29290583 |pmc=5975648 }}</ref> and [[steroids]]. Cells which secrete these products, such as those in the [[testes]], [[ovaries]], and [[sebaceous gland]]s have an abundance of smooth endoplasmic reticulum.<ref>{{cite news|title=Functions of Smooth ER|publisher=University of Minnesota Duluth}}<!--|access-date=16 December 2012--></ref> It also carries out the metabolism of carbohydrates, detoxification of natural metabolism products and of alcohol and drugs, attachment of receptors on cell membrane proteins, and [[steroid metabolism]].<ref>{{cite journal | vauthors = Maxfield FR, Wüstner D | title = Intracellular cholesterol transport | journal = The Journal of Clinical Investigation | volume = 110 | issue = 7 | pages = 891–8 | date = October 2002 | pmid = 12370264 | pmc = 151159 | doi = 10.1172/JCI16500 }}</ref> In muscle cells, it regulates [[Calcium in biology|calcium ion]] concentration. 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 is connected to the [[nuclear envelope]] and consists of tubules that are located near the cell periphery. These tubes sometimes branch forming a network that is reticular in appearance.<ref name="Shibata-2006" /> In some cells, there are dilated areas like the sacs of rough endoplasmic reticulum. The network of smooth endoplasmic reticulum allows for an increased surface area to be devoted to the action or storage of key enzymes and the products of these enzymes.{{cn|date=December 2023}}

==== Sarcoplasmic reticulum ====
[[File:Blausen 0801 SkeletalMuscle.png|thumb|left|250px|[[Skeletal muscle]] fiber, with sarcoplasmic reticulum colored in blue]]
{{main|Sarcoplasmic reticulum}}
{{See also |Calcium-induced calcium release}}

The sarcoplasmic reticulum (SR), from the Greek σάρξ ''sarx'' ("flesh"), is smooth ER found in [[muscle cell]]s.  The only structural difference between this organelle and the smooth endoplasmic reticulum is the composition 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 calcium ions and pumps them out into the sarcoplasm when the muscle fiber is stimulated.<ref name="Toyoshima-2000">{{cite journal | vauthors = Toyoshima C, Nakasako M, Nomura H, Ogawa H | title = Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution | journal = Nature | volume = 405 | issue = 6787 | pages = 647–55 | date = June 2000 | pmid = 10864315 | doi = 10.1038/35015017 | bibcode = 2000Natur.405..647T | s2cid = 4316039 }}</ref><ref>{{cite book | first = Steven R | last = Goodman | name-list-style = vanc | title = Medical Cell Biology | edition = 3rd|publisher=Academic Press|pages=69|url=https://books.google.com/books?id=tRbCHk9easQC&q=smooth+er+stores+calcium+ions+muscle+cells&pg=PA69 | isbn = 9780080919317 | date = 2007-11-26 }}</ref> After their release from the sarcoplasmic reticulum, calcium ions interact with contractile proteins that utilize ATP to shorten the muscle fiber. The sarcoplasmic reticulum plays a major role in [[excitation-contraction coupling]].<ref>{{cite book |title = Fundamentals of Anatomy and Physiology |first1 = Frederick |last1 = Martini |first2 = Judi |last2 = Nath |first3 = Edwin |last3 = Bartholomew | name-list-style = vanc |edition = 10th |isbn = 978-0321909077 |year = 2014|publisher = Pearson }}</ref>