Editing Endoplasmic reticulum (section)

===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.