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Transcript of Endoplasmic Reticulum
Quality Control Function The Endoplasmic Reticulum - The endoplasmic reticulum (ER)is the largest internal membrane in a cell .
- It consists of a network of interconnected flattened membrane bound sacs and tubules that extends
throughout the cytosol, known as the cisternae.
- These tubules and sacs interconnect and form a continuous sheet, enclosing the ER lumen and
separating it from the cytosol . The lumen of the ER can comprise 10% of the total cell
volume . The ER is a motile structure, and uses motor proteins such as kinesins to move along the microtubules.
- The ER membrane is continuous with the outer nuclear membrane . The membrane of the ER is
permeable and allows small molecules to travel through .
- In most cells, the ER is divided into two regions, the rough endoplasmic reticulum (RER) and the
smooth endoplasmic reticulum (SER), both of which are designed to carry out a specific function .
- The ratio of the amount of SER to RER in each cell differs considerably depending on the type of cell, and the function that that cell carries out . Rou E n d o p l as mic Structure - The rough endoplasmic reticulum (RER) is studded with ribosomes  along its cytosolic membrane.
- The RER is granular in texture .
- The gel like lumen of the ER has a different composition from the cytosol, the protein and gluthione thiols are more oxidised, and there is a separate pyridine nucleotide pool. The activity of some of the enzymes in the lumen is dependent on the transport of the specific substrates and co-factors across from the cytosol, therefore their transport is essential.
- The RER is thought to be sepeated into domains, classified by the number of membrane-bound ribosomes, along with the RNA, cholesterol and phospholipid content of the regions of the RER . The RER contains many different protens, e.g. glycosylation enzymes, chaperones and mutation proteins. [7}
- The RER structure is closely related to its function .
- The RER lumen favours folding and assembly of proteins. Cells that secrete large amounts of proteins have large regions of RER e.g. acinar cells in the pancreas . The RER has a large surface area for ribosomes to attach- there are 13 million ribosomes per cell .
For a comprehensive overview see Voeltz, G. K., Rolls, M. M. and Rapoport, T. A. (2002). Structural organization of the endoplasmic reticulum. EMBO Reports 3:944-950.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1307613/ Other text. Protein Synthesis Protein Trafficking Glycosylation Membrane Synthesis Ret icu lum gh Summary S m o o t h E n d o p l a s m i c Sterol Synthesis Calcium Signalling Lipid Elongation In comparison to RER, the smooth endoplasmic reticulum (SER) has a much curvier, more tubular shape, with a smoother surface due to the absence of ribosomes on its outer surface . In some types of cell, such as sea urchin eggs, the SER forms flat sheets. It’s not entirely understood how the two ERs maintain distinct protein compositions as the luminal spaces are continuous. It is probable that the different membrane proteins are tightly fixed in their particular domains, thus allowing different sections of ER to have different functions .
The SER is found extensively in liver cells, kidney tubules, cardiac and skeletal muscle,
and steroid-producing endocrine glands. The principal function of the SER is different in
each cell type.
-In kidney cells and hepatocytes, the ER is specialised for the detoxification of hydrophobic
-Neurone ER is important for calcium regulation
-In endocrine glands, the ER is primarily involved in the synthesis of steroid hormones
-Muscle cells contain a form of ER called sarcoplasmic reticulum (SR), which is
significant in muscle contraction 
Transitional endoplasmic reticulum (TER) is a another specialised type of SER, which packages proteins ready for transport to the golgi apparatus .
The SER is also present in plants, where it acts as a store for proteins and lipids (16). Furthermore, it has been suggested that the SER provides a back-up store of calcium to minimise the risk of deficiency, as calcium has important signalling and structural roles in plant cells [17,18]. Drug Detoxification •Very long chain fatty acids (VLCFA) of up to 26 carbons in length are formed by the elongation of shorter fatty acids, usually 16 and 18 carbons long .
•Major difference between the elongation and synthesis processes is that CoA is used as an acyl carrier instead of an acyl carrier protein
•Follows a cyclic series of reactions – condensation, reduction, dehydration and a second reduction [28, 29].
•The condensation of the acyl part of the fatty acid with malonyl CoA to produce a 3-ketoacyl CoA. Achieved by ELO proteins. ELO proteins show a distinct tissue distribution as well as a varying specificity for certain substrates [28, 29].
•The reduction of the 3-ketoacyl-CoA to a 3-hydroxyacyl CoA molecule is catalysed by a homologue of the Ybr159p protein that is found in yeast .
•The dehydration of the 3-hydroxyacyl CoA to an enoyl CoA molecule is carried out by 3-hydroxyacyl-CoA dehydratase (HACD). HACD also shows specific expression and distribution in certain tissue types. HACD1 and HACD4 are seen in high levels in both the heart and in leukocytes where as HACD2 and HACD3 are expressed ubiquitously. This suggests that HACD and ELO are linked and that HACD protein also have specific substrate preferences, although this has not yet been proven .
•The final reduction of the enoyl CoA in mammals is catalysed by the homologue of the yeast protein Tsc13p. Trans 2,3-enoyl CoA reductase (TER) are unusual as they do not contain an ER retention site whereas the other 3 enzymes do. 2 variations have been found in mammals, KAR and TER [28, 29]. R e t i c u l u m * Nearly all proteins produced on membrane-bound ribosomes become glycoproteins .
* Most common form is N-glycosylation. It is dependent on protein conformation.
* Polypeptides entering the lumen are glycosylated at aspargine residues (11) on the NH2 group by the enzyme oligosaccharide transferase, the active site on the lumenal side of the membrane .
* The oligosaccharide is a high mannose chain & is transferred en bloc. This high mannose chain is in close relation to the ER membrane .
* Dolichol is the lipid molecule which holds the oligosaccharide in place in the membrane by a high energy pyrophosphate bond, this provides energy to drive the reaction.
* Immediately after amino acid enters the lumen during translocation the oligosaccharide transfers it to aspargine in one enzymatic step.
* The oligosaccharide is a built up sugar by sugar on the membrane bound lipid molecule by the enzyme glycosyltransferases in RER membrane.
* Nucleotide sugars in the cytosol activate these sugars & donate the sugar to the lipid halfway through the lipid linked oligosaccharide.
* This flips into the lumen where 3 glucose & a mannose removed .
* Carbohydrate groups act as binding sites on glycoproteins to interact with other macromolecules in cellular processes & aid folding of proteins . * The RER is studded with many membrane bound ribosomes which is the major site of protein synthesis. Two types of ribosomes exist, those that are free it in cytosol, and those bound to the RER. The ribosomes that are bound to the ER translate their amino acid sequences and then insert them into the lumen of the ER.
* During protein synthesis, the ER captures some of the proteins from the cytosol. There are two types of proteins that are captured by the ER, those that are only partially transported across the membrane, trans-membrane proteins, and water-soluble proteins, that are fully transported across the membrane into the ER lumen .
* Before the polypeptide chain is completely synthesized, the import of proteins into the ER begins. It is a co-translational process. Whilst the polypeptide chain in being assembled, the other end is embedded within the ER. This ensures no protein folding takes place.
* A variety of enzymes act on the polypeptide whilst it is in the ER. The N-terminal is usually removed by a proteolytic enzyme called signal peptidase & an oligosaccharyltransferase adds a carbohydrate.
* In the lumen molecular chaperones recognise & bind to unfolded or mis-folded proteins where they can attain a 3D structure. Enzymes such as protein disulphide isomerise then process the proteins .
* The RER synthesis proteins such as those produces by the secretory cells, e.g. the digestive enzymes and hormones such as insulin that are produced by the pancreas.
The RER also synthesises intergral membrane proteins and soluble proteins. Quality Control * After the proteins have been synthesised within the RER they must be transported to many different locations, including other intracellular organelles, extracellular release and incorporation into the plasma membrane.
* To achieve this each protein contains a specific ‘tag’ which labels it as a target for inclusion into transport vesicles. These tags can be in the form of a number of different structural features, e.g. specific amino acid sequences or hydrophobic domains, depending on the protein type and its destination .
* The ER must also be able to trap some of the proteins it synthesises. This residency is achieved in two ways; the first is through the prevention of proteins from entering transport vesicles and the second is through retrieval of any proteins that have escaped.
* Retrieval is controlled by discrete retrieval motifs whose structures vary according to the protein type to which they are tagged. For example, Soluble proteins have a H/KDEL sequence located at their carboxy – terminus and membrane proteins have a either a di-lysine or a di-argenine located close to their cytoplasmic domain terminus . * The ER acts as a site for the quality control of newly synthesised proteins ensuring only correctly assembled oligomers are retained and those which are persistently misfolded are degraded  by cytosolic proteases .
* Misfolding of proteins can be detrimental to cells and is known to contribute to many inherited disorders, e.g. Cystic Fibrosis .
* A primary constituent of the quality control mechanism is UDP- glucose:glycoprotein glucotransferase which is a sensor within the calnexin/calreticulin (CNX/CRT) cycle .
* Calnexin (membrane bound ER protein) and Calreticulin (soluble) promote disulphide bond formation by forming a complex with the newly formed glycoprotein and ERp57 (a thiol oxidoreductase)
* This protein complex then dissociates and a glucose unit is removed from the glycoprotein by the enzyme glucosidase II  therefore making it unrecognisable to the CNX/CRT cycle .
* UGGT then binds to any improperly folded proteins and adds back a single glucose unit. Consequently the protein once again becomes a substrate for another round of CNX/CRT binding and disulphide bond reformation.
* Once the correct conformation is achieved, the UGGT no longer binds to the glycoprotein and it is free to leave the ER and translocate to the Golgi . - In smooth and skeletal muscle, the smooth endoplasmic reticulum takes the form of sarcoplasmic reticulum (SR), from which the release of stored calcium ions into the cytosol triggers muscle contraction .
Muscle Contraction and the Smooth Endoplasmic Reticulum
- Protein labelling has shown that the SR forms a tight system of loops around contractile fibrils, and is closely associated with the network of T-tubules (invaginations of the sarcolemma that ensure rapid depolarisation deep into the muscle fibre and thus ensure synchronised muscle contraction) .
- Muscle contraction is triggered by a process called calcium-induced calcium release (CICR), where a local increase in calcium level is amplified by calcium release from stores [23,24]. As the action potential travelling down the motor neurone reaches the t-tubule, voltage-gated L-type Ca2+ channels are opened, allowing influx of calcium into the SR. Also opened are ryanodine receptors (RyR) in the SR membrane, which causes calcium to be released into the cytosol. The calcium then binds to troponin, and muscle contraction is triggered .
- The sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) protein in the SR membrane pumps Ca2+ from the muscle cytosol back into the lumen of the SR against its concentration gradient, using ATP .
- It has recently been suggested that calcium is also involved in the structure of ER and in the regulation of ER luminal proteins, and that calcium stores are also present in non-muscle SER .
For a comprehensive overview see:
Koch, G. L. E. (1990), The endoplasmic reticulum and calcium storage. Bioessays, 12: 527–531. doi: 10.1002/bies.950121105
http://onlinelibrary.wiley.com/doi/10.1002/bies.950121105/abstract •Smooth endoplasmic reticulum is more prevalent in liver cells due to their detoxification role .
•Stores and modifies cytochrome P450 enzymes - The lipophilic environment of the smooth ER walls combined with the high lipid concentration caused by lipid synthesis causes any lipophilic molecules to flow along the ER walls towards the cytochrome P450 .
•At the cytochrome P450 enzymes the water insoluble toxic substances are usually modified into water soluble substances and then excreted through the renal pathway .
The smooth endoplasmic reticulum proliferates in the presence of foreign toxins and is broken down by a lysozome-based process . SER Introduction Figure 1. TEM images of endoplasmic reticulum, visualised by epifluorescence microscopy
(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1307613/figure/f1/ October 2002) RER and SER are
interconnected and continuous! Extra Material Here's a few links to some more information you might find helpful.
YouTube video of the ER in a living plant cell http://www.youtube.com/watch?v=7PGRC5Se36
Here's a link to a review of the structure of ER: Structural Organisation of the endoplasmic reticulum
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1307613/ Figure 5. Video of the dynamic properties of the endoplasmic reticulum in a living plant cell
http://www.youtube.com/watch?feature=player_embedded&v=7PGRC5Se36k, 2012 Why is the SER prominent in liver cells? What enzyme is present? Catalyses the final reduction of enoyl CoA in mammals What does the homologue of the yeast protein Tsc13p do in lipid elongation? Smooth ER Because of their detoxification role by the enzyme cytochrome P450. What and where is the enzyme that catalyses the addition of sugars to the oligosaccharide in N-glycosylation? NH2 on Asparagine residues What part of the polypeptide is glycosylated? Protein disulphide isomerase What is an example of an enzyme that processes proteins in protein synthesis? Glycosyltransferases in the RER membrane Endoplasmic
Quiz Name and describe the mechanism by which calcium is released from SR to induce muscle contraction. • CICR- Calcium Induced Calcium Release
• Action potential down motor neurone; conducted down t-tubules deep into muscle fibres; opens voltage gated Ca2+ channels in SR: calcium into SR. RyR opened: calcium out of SR into cytosol.
• Ca2+ binds to troponin… Muscle contraction process (look up the Sliding Filament Theory for more info here!) Liver, kidney, neurones, muscle (skeletal and cardiac),
endocrine In which types of cell is SER predominantly found? Insig, SREBP, SREBP cleavage-activating protein (SCAP) Name the 3 polytopic proteins involved in the sterol synthesis pathway. Describe UDP – glucose glycoprotein glucotransferase (UGGT) A sensor in the within the calnexin/ calreticulin (CNX/CRT) cycle.
It binds to incorrectly folded proteins and adds back a single glucose unit therefore once again making the protein a substrate for another round of CNX/CRT binding. Protein retrieval is controlled by discrete retrieval motifs, which motif type would be bound to a membrane bound protein? A di-lysine or di-arginine located close to their cytoplasmic domain terminus. By the number of membrane bound ribosomes, and the RNA, cholesterol and phospholipid content of the RER. Ribosomes Cisternae How are the domains of the RER classified? What is found in abundance along the cytosolic side of the RER membrane? What are the names of the membrane bound sacs found in the cytosol of the endoplasmic reticulum? Rough ER So, we hope you've been following... Now test yourself! Figure 2. A coloured TEM of the RER, showing long membrane-bound vesicles (pink) bearing ribosomes (black dots) on the outer surface. The membrane is continuous with the nuclear membrane (bottom edge, dark grey). Magnification x25,800. (http://www.sciencephoto.com/media/214947/view 2012) The endoplasmic reticulum (present in most eukaryotic cells) is a continuous network of tubules which spans the entire cell, and is closely connected to the nuclear membrane.
ER is subdivided into rough ER and smooth ER. The RER is involved in protein synthesis, modification, trafficking, and quality control. The SER is involved in calcium storage and release, lipid and steroid synthesis, and detoxification of foreign substances.
The ratio of RER to SER in a cell varies depending on tissue type, therefore allowing the development of highly specialised cell types. Bored yet? Here's a nice video for you... •The first method of regulation involves the inhibition of the sterol regulatory element binding protein (SREBP) pathway, which in turn inhibits transcription of the HMGCR gene. The pathway consists of 3 polytopic proteins, Insig, SREBP, and SREBP cleavage-activating protein (SCAP). When sterol levels are high the SCAPs sensing domain changes shape and associates with Insig, rather than transporting SREBP to the golgi. The SREBP precursor is therefore unable to act as transcription factor .
The second method is by encouraging HMGCR degradation. High sterol levels cause HMGCR to bind Insig which further binds ubiquitin, which directs the enzyme to proteasomes that degrade it . Figure 7: A simplified diagram showing the various feedback mechanisms of the cholesterol synthesis pathway
http://www.nature.com/clpt/journal/v90/n6/fig_tab/clpt2011215f2.html (2011) This is one of them...Looks complicated doesn't it? •SER fluctuations in response to hormones suggests the close regulation of both the synthesis and degradation of HMGCR and other enzymes involved in the synthesis of cholesterol and other steroid hormones . Almost finished, honest! 1 - Lodish, H., Kalsai, C., Bretscher, A., Amon, A., Berk, A., Kreiger, M., Ploeugh, H. et al. (2000). Molecular Cell Biology. New York: W.H.Freeman and Company
2 - Johnsons, A and Lewis, J and Raff, M and Alberts, B and Roberts, K. 2002. Molecular biology of the cell. New York: garland science.
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4- Bolsover, S., Shephard, E., White, H. and Hyams, J. (2011). Cell Biology: A short course. 3rd ed. New Jersey: Wiley-Blackwell.
5- Pryme, I. F. (1989). Domains of rough endoplasmic reticulum. Molecular and Cellular Biochemistry 87:93-103.
6 - Voeltz, G. K., Rolls, M. M. and Rapoport, T. A. (2002). Structural organization of the endoplasmic reticulum. EMBO Reports 3:944-950.
7 - Karp, G. (2010). Cell Biology. 6th Edition
8- Becker, W., Kleinsmith, L. and Hardin, J. (2005). The World of the Cell. 6th ed. San Fransisco: Pearson.
9- Rapoport, T. A. (1992). Transport of proteins across the ER Membrane. Science 258:931-336.
10 - Teasdale, R and Jackson, M. 1996. Signal mediated sorting of membrane proteins between the ER and the Golgi. Cell and developmental biology. 12, 27-54.
11 - Vitale, A., Ceriotti, A., and Denecke, J. (1993). The role of the endoplasmic reticulum in protein synthesis, modification and intracellular transport. Journal of Experimental Botany. 44:1417-1444
12 - Ellgard, A and Helenius, A. 2003. Quality control in the Endoplasmic reticulum. National review of molecular biology. 4(3) 181-191.
13 - Orgensen, J and Bross, P and Gregersen, N. 2003. Protein quality control in the Endpolasmic reticulum. APMIS supplement. 109, 86 -91.
14 - Pejgaard, S and Nicolay, J and Taher, M and Thomas, D and Bergeron, J. 2004. The endoplasmic reticulum glycoprotein quality control system. Molecular biology. 6, 29-42.
15. Voeltz, G.K., Rolls, M.M., Rapoport, T.A. (2002), Structural organization of the endoplasmic reticulum. EMBO Reports, 3(10): 944–950. doi: 10.1093/embo-reports/kvf202
16. Denecke, Jurgen(Apr 2001) Plant Endoplasmic Reticulum. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001673]
17. Dayod, M., Tyerman, S. D., Leigh, R.A., Gilliham, M. (2010), Calcium storage in plants and the implications for calcium biofortification. Protoplasma, 247:215–231. doi: 10.1007/s00709-010-0182-0
18. Gilliham M., Dayod, M., Hocking, B.J., Xu, B., Conn, S.J., Kaiser, B.N., Leigh, R.A., Tyerman, S.D. (2011), Calcium delivery and storage in plant leaves: exploring the link with water flow. Journal of Experimental Botany, 62 (7): 2233-2250. doi: 10.1093/jxb/err111
19. : Black, V.H., Sanjay, A., van Leyen, K., Lauring, B and Kreibich, G. (2005) Cholesterol and Steroid Synthesizing Smooth Endoplasmic Reticulum of Adrenocortical Cells Contains High Levels of Proteins Associated with the Translocation Channel. Endocrinology 146: 4234–4249
20. Auchus, R.J. and Adams, C.M. (2005) Cholesterol, Steroid and Isoprenoid Biosynthesis. In: Encyclopaedia of Life Sciences [Online]. Available at: http://www.els.net/WileyCDA/ElsArticle/refId-a0001393.html [Accessed 15/11/2012]
21. 6.Squire, John M(Oct 2010) Muscle Contraction: Regulation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000674.pub2]
22. Jayasinghe, I., Crossman, D., Soeller, C. and Cannell, M. (2012), Comparison of the organization of t-tubules, sarcoplasmic reticulum and ryanodine receptors in rat and human ventricular myocardium. Clinical and Experimental Pharmacology and Physiology, 39: 469–476. doi: 10.1111/j.1440-1681.2011.05578
23. Endo, M. (2009), Calcium-induced calcium release in skeletal muscle. Physiological Reviews. 89(4):1153-76
24. Sandler, V.M., Barbara, J.G. (1999). Calcium-Induced Calcium Release Contributes to Action Potential-Evoked Calcium Transients in Hippocampal CA1 Pyramidal Neurons. The Journal of Neuroscience, 19(11): 4325-4336
25. Kekenes-Huskey, P.M., Metzger, V.T., Grant, B.J., McCammon, A.J. (2012), Calcium binding and allosteric signalling mechanisms for the sarcoplasmic reticulum Ca(2+) ATPase. Protein Sci., 21(10):1429-43. doi: 10.1002/pro.2129
26. Koch, G. L. E. (1990), The endoplasmic reticulum and calcium storage. Bioessays, 12: 527–531. doi: 10.1002/bies.950121105
27. Coleman, Michael. Human drug metabolism: an introduction. Wiley, 2010.
28. Tehlivets, O., Scheuringer, S., Kohlwein, S.D. (2007). Fatty acid synthesis and elongation in yeast. Biochimica et Biophysica Acta 1771:255–270
29. Uchida, Y. (2011). The role of fatty acid elongation in epidermal structure and function. Dermato-Endocrinology 3:65-69 Figure 6: Simplified diagram showing the inhibition of the sterol regulatory element binding protein (SREBP) pathway
http://www.jbc.org/content/280/28.cover-expansion (2005) Figure 8: Diagram showing the various ER architecture and membrane components in different cell types.
http://endo.endojournals.org/content/146/10/4234(2005) Now Test Yourself! Thanks
watching! Reference List Figure 3: Shows steps of protein synthesis (http://teachmix.com/filmwriting/content/drama-protein-dna-function 2010) Figure 4: A video showing general RER overview, with particular focus on protein translocation, which you've just read about! (http://www.youtube.com/watch?v=PUy_Em5dXmc) Figure 9: A video summarising ER (2012) URL: http://wwww.youtube.com/watch?v=faE3STnflGs&feature=endscreen&NR=1 To break it down for you, here's a summary of RER vs SER And let's not forget that some people really like plants... Figure 3 shows protein synthesis which include:
- Nascent polypeptides have a signal sequence
- This signal sequence binds the signal recognition particle (SRP)
- Polypeptides and ribosomes bind to the SRP which stops translation.
- The SRP binds to the SRP receptor, and the ribosome binds to the Translocon, which binds the protein to the ER membrane
- The SRP is released
- Translation resumes when the hydrophobic signal sequence joins to the Translocon. And one final function... Membrane Biosynthesis - Membranes are not usually synthesized from scratch, rather they arise from pre existing membranes.
- The integral membranes of the ER synthesise these membranes.
- The Active sites of the proteins face out to the cytosol away from the ER lumen.
- Phospholipids are then inserted into the cytosolic face and are made to revert to the luminal face.
- Further modification to the enzymes takes place through out the cell. (7) There are a number of membrane-bound regions in the translocon which move with the protein.
There are 10 spans for the alpha domain, 1 transmembrane spans in the beta, and 1 in the gamma.
There is a belt of hydrophobic molecules around the side of the translocon that sqeeze it together- this allows a plug to form in the middle, i.e. it blocks the translocon.
Ribosome binding causes a conformational change and the pore becomes unblocked (7). How To use a Prezi To make your way through this Prezi simply click the forward button which will guide you through the Endoplasmic Reticulum. You can use the bar at the bottom of the page to see an overview of where you are in the Prezi, and to more easily skip between different sections.
Key words and concepts have been highlighted in a different colour to draw your attention to important facts.
After making your way to the end test yourself in our quiz.
There are also some sample essay questions to help with revision. Rough Endoplasmic Reticulum Nucleus Translocation of proteins into the ER lumen Cholesterol binds Scap, which in turn binds Insig Cholesterol "Compare and contrast the structure of both the smooth and rough endoplasmic reticulum"
"Compare and contract the functions of both the rough and smooth endoplasmic reticulum"
"Describe the role of the rough endoplasmic reticulum in protein synthesis"
"Describe the role the smooth endoplasmic reticulum plays in both cholesterol synthesis and drug detoxification" Potential Essay Question Vitale, A., Ceriotti, A., and Denecke, J. (1993). The role of the endoplasmic reticulum in protein synthesis, modification and intracellular transport. Journal of Experimental Botany. 44:1417-1444
http://jxb.oxfordjournals.org/content/44/9/1417 A journal which provides a summary of protein synthesis: By the end of this section on the Rough Endoplasmic Reticulum you should know...
- The structure of the RER
- The different functions of the RER
- Protein Synthesis
- Protein trafficking
- Quality Control
- Membrane Biosynthesis
If you know these key point then you should be able to answer any question that the exam throws at you about the rough endoplasmic reticulum!
To test yourself further, try the example essay questions at the end of the prezi! In There is a large concentration of SER compared to RER within steroid secreting cells such as the ovaries, testes and the adrenal glands. The quantity and structure of the SER varies depending on hormonal stimulation .
The Mechanism of Sterol Synthesis
•Acetoacetyl CoA is first formed by the condensation of 2 molecules of acetyl CoA by the enzyme acetoacetyl–CoA acyltransferase before 3-hydroxy-3-methylglutaryl (HMG) CoA synthase adds the third to make HMG CoA .
-HMG CoA reductase (HMGCR) then catalyses the reduction of the ester to form mevalonate. This step is the rate limiting step in the process. 2 forms of HMGCR exist, class I enzymes in eukaryotes and class II enzymes in prokaryotes. Class I enzymes vary from class II in their N terminal membrane attachment domains which are involved in the regulation of the enzyme. They tend to have large domains whereas class II enzymes do not.
- The mammalian enzyme, a class I enzyme, has 8 segments that span the membrane of the SER in addition to a cytosolic C terminal domain that is catalytic in nature .
-HMGCR affects both the rate of cholesterol synthesis and the structure of the SER. Overexpression causes the more complex forms of the SER to develop, such as the more crystalloid structure [19,20].
-Sterols are actually able to apply direct inhibition on HMGCR. This in turn regulates the levels of sterols present within the SER. Two primary mechanisms are used [19,20]. Methods of Regulating of Sterol synthesis Rough Endoplasmic Reticulum Summary The structure and function of endoplasmic reticulum!