Prezi

Present Remotely

Send the link below via email or IM

Copy

Present to your audience

Start remote presentation

  • Invited audience members will follow you as you navigate and present
  • People invited to a presentation do not need a Prezi account
  • This link expires 10 minutes after you close the presentation
  • A maximum of 30 users can follow your presentation
  • Learn more about this feature in the manual

Do you really want to delete this prezi?

Neither you, nor the coeditors you shared it with will be able to recover it again.

DeleteCancel

Make your likes visible on Facebook?

Connect your Facebook account to Prezi and let your likes appear on your timeline.
You can change this under Settings & Account at any time.

No, thanks

The Structure & Function of the Rough and Smooth Endoplasmic Reticulum

BI2202 - Advanced Cell and Immuno Biology
by BI2202 Group 20 on 1 February 2013

Comments (0)

Please log in to add your comment.

Report abuse

Transcript of The Structure & Function of the Rough and Smooth Endoplasmic Reticulum

If a polypeptide is translocated into the ER from a membrane bound ribosome it is known as co-translational translocation [3].

The folding of a polypeptide into its correct three dimensional protein structure is mediated by molecular chaperones [2.3].

Chaperones bind to unfolded polypeptides, stabilising them to prevent incorrect
folding [2,3]. One of the primary chaperone proteins is binding immunoglobulin protein
(BiP: Figure 4). BiP belongs to a heat sensitive protein family (Hsp70) and has both a protein
binding and an ATPase domain [3,6]. BiP is also used to seal the translocon pore when not
occupied by a ribosome [6].

If a polypeptide is incorporated into the ER from a free ribosome it is known as post-translational translocation [3]. INTRODUCTION The endoplasmic reticulum is a membranous organelle which is found in all eukaryotic cells [2,5] and comprises half of its total membrane area, as well as occupying 10% of the total cell volume [3,4]. The ER is a system of branching tubules and flattened sacs which extend throughout the cytosol [2]. It is continuous with the outer nuclear membrane [2,5,12].

The endoplasmic reticulum is the largest organelle in a eukaryotic cell [3]. Within the membrane is the ER lumen or the ER cisternal space which differs greatly from the cytosolic space [2].

The ER has many different functions, including:
Translocation of proteins (such as secretory proteins) across the ER membrane [2,4]
Integration of proteins into the plasma membrane [21]
Folding and modification of proteins in the ER lumen [2,4]
Synthesis of phospholipids and steroids on the cytosolic side of the ER membrane [2,4]
Storage of calcium ion in the lumen and their regulated release into the cytosol [2,4]
Carbohydrate metabolism [4]

The main advantage of having an endoplasmic reticulum is that it provides a separate chemical environment which allows for correct protein folding. Smooth Endoplasmic Reticulum The smooth endoplasmic reticulum is highly curved and tubular [12]. It forms an interconnecting system of pipelines which form a network throughout the cytoplasm [12].

The lipid composition of the ER membrane is different to that of other cell compartments. It has a large abundance of phosphatidylcholine and a very low concentration of cholesterol. It is also very fluid and discorded due to its large proportion of unsaturated fatty acids [4]. INTERESTING FACT! In plant cells, the ER forms one continuum throughout the plant, via tubular connections between adjacent cells called plasmodesmata [5]. The smooth endoplasmic reticulum is more prominent in some cells than in others, depending on cell function [2].

One cell type that contains a large quantity of smooth ER is the hepatocyte. Found in the liver, these cells are heavily involved in processes that take place in the smooth ER so need an expanded ER to accommodate more enzymes [2]. Some examples of hepatocyte function include:
Lipid and lipoprotein production [12]
Lipid metabolism [2]
Detoxification of lipid-soluble drugs [12]
Steroid production and hormone synthesis (also occurs in endocrine cells) [12]

The endoplasmic reticulum synthesises nearly all of the major classes of lipids, (including phospholipids and cholesterol), but their main product is phosphatidylcholine [2]. The enzymes are in the ER membrane facing the cytosol where their substrates are present [2].

The smooth endoplasmic reticulum sequesters almost all of the Ca from the cytosol [2,12]. More Smooth Endoplasmic Reticulum 2+ The smooth ER sequesters Ca2+ ions from the cytosol for storage in the ER lumen. This is achieved via a Ca2+ pump and high concentrations of calcium-binding proteins within the lumen. The endoplasmic reticulum membrane is also poorly permeable to calcium ions which stops them from leaking back into the cytosol. Some cells have smooth ER further specialised that is dedicated to the release and reuptake of Ca2+. Calcium ion release and reuptake also occurs in response to extracellular signals [2,4,12,18]. Some cells have smooth ER further specialised that is dedicated to the release and reuptake of Ca2+. The most widely used example of this is the sarcoplasmic reticulum, found in muscle cells. Calcium ion release and reuptake triggers myofibril contraction and relaxation respectively in muscle [2,4,12,18]. INTERESTING FACT! There have been several experiments which have provided evidence that the ER is a single membrane system with a continuous intraluminal space [22]. The Structure of the Rough Endoplasmic Reticulum The lipid composition of the rough ER is similar to that of the smooth [4]. Unlike smooth ER, rough ER is composed of flattened sacs [2] and has abundant translocon pores [5]. Ribosomes are free to attach at these sites to synthesise proteins and transport them directly into the ER lumen, after which the ribosomes can detach [5]. The presence of ribosomes studded on the membrane is what gives the rough ER its name [2]. The Function of the Rough Endoplasmic Reticulum The rough ER has roles in:
- Protein folding [3,4]
- Assembly of multi-subunit proteins [3]
- Disulphide bond formation [3]
This requires an oxidising environment whereas the cytosol provides a reducing environment. An oxidising environment is found within the ER lumen which also contains disulphide isomerase, an enzyme which facilitates disulphide bond formation.
- Glycosylation [2,3]
The initial stages of glycosylation occur on specific asparagine residues through the calnexin/calreticulin cycle [18].
- Degradation of misfolded proteins through the ubiquitin proteasome pathway [1] Formation of Tertiary Structure in Proteins If a protein fails to fold correctly, it is marked for degredation. This process involves BiP, other chaperone proteins, protein disulphide isomerase and other supporting proteins.

If high levels of misfolded proteins are detected, the competition for BiP triggers a stress response (the unfolded protein response). This leads to inhibition of protein synthesis, increased expression of chaperones and an increase in the degradation of secretory pathway mRNAs.

This response halts protein production and synthesises more chaperones which can help to destroy or revive the high volume of misfolded proteins. If these steps do not decrease the levels of misfolded proteins, apoptosis is induced, destroying the affected cell [1]. Misfolded Proteins: The Ubiquitin Proteasome Pathway INTERESTING FACT! The role of rough endoplasmic reticulum in protein processing and sorting was first discovered in the 1960s by George Palade [3]. A Comparison of the Rough and Smooth Endoplasmic Reticulum
Eukaryotic cells are believed to be the result of an endosymbiotic event whereby an anaerobic archaeon engulfed an aerobic bacterium. The bacterium evolved into today's mitochondria.

Archaeal membranes and bacterial membranes are different in lipid composition so we would expect to find that, in eukaryotes, all membranes apart from mitochondrial membranes to be like archaeal membranes.

However, eukaryotes have membranes that are uniformly bacterial, both in lipid structure and in many details of their embedded proteins!

In fact, in eukaryotes there is no trace of the original archaeal membranes despite the fact that other features point to the original host cell almost certainly being an archaeon (for example, histone proteins are found only in eukaryotes and some archaea, not in bacteria).

HOW might this have happened?! [15] The Origin of the Endoplasmic Reticulum The rough ER exports folded proteins within vesicles via the secretory pathway:
Rough ER --> Golgi apparatus --> Secretory vesicles --> Target [3]

This transport is bidirectional; it allows for the recycling of valuable, soluble proteins such as BiP. There are retention signals on BiP which signal the Golgi to initiate retrograde transport back to the ER [7].

This process is driven by a protein-protein interaction on the cytosolic face of the ER membrane. Once a vesicle carrying BiP is formed, a coat of COPII proteins cover the vesicle and guide it towards the Golgi. A group of proteins called SNAREs then mediate the de-coating process, which is associated with GTP hydrolysis. The de-coating process must occur in order for the Golgi to recognise the vesicle membrane, ensuring that the subsequent fusion of membranes is with the correct target membrane [7]. Secretory Pathway Calnexin and calreticulin are two homologous lectin chaperone molecules that carry monoglucosylated N-linked glycans to proteins awaiting glycosylation in the ER. The mechanism of this is shown to the right. For simplicity only calreticulin is shown.

The purpose of this cycle is not only to add a specific oligosaccharide to a protein to allow for its function, but also to allow for the permanent marking of proteins that are mis-folded (see Figure 5).

Glycosylation: Calnexin/Calreticulin Cycle This may have occurred due to gene transfer from mitochondria to the host cell. However, the host cell may have been unable to target the protein products to a particular cell location, resulting in a situation where the host cell can MAKE bacterial products but doesn't 'know' what to do with them.

Because they aren't water soluble, untargeted lipids resulting from these untargeted proteins would coalesce. Lipid droplets tend to fuse, forming enclosed membranous structures. This could have happened close to where they were first formed (such as around the chromosomes) forming loose membranous structures, similar to the eukaryotic nuclear membrane. Further expansion of these lipids may have resulted in other membranous structures such as vesicles, the Golgi complex and of course the endoplasmic reticulum.

These bacterial lipids may have been selected for in the host cell due to better fluidity and adaptability.

Today's steroids, hormones, vitamins and some other polymers provide further evidence for the gene transfer hypothesis explaining bacterial membranes in eukaryotes. These structures are isoprenoids, which are structures made up of linked isoprenes. Isoproenes are the basic building blocks of archaeal lipids, and most eukaryotes still have the genes to make them, even though they are not used for eukaryotic membranes [15]. The Origin of the Endoplasmic Reticulum Protein Secretion from the ER For basic background information on the ER, watch this video (one of a series of educational videos found on YouTube) from 2 minutes onwards [19]. Figure 3. A scanning electron micrograph of the smooth endoplasmic reticulum from an adrenal cortical cell. This cell type has an abundance of smooth ER to accommodate steroid production [8]. Membrane sac of the smooth ER Free ribosomes Ribosomes bound to the rough ER INTERESTING FACT! The word "reticulum" is a synonym for "network" [2]. Figure 1. An image to show the extent of the ER (green) throughout the cell, visualised with fluorescence microscopy [10].

Click on the following link to see the above image in action:
http://learn.hamamatsu.com/galleries/digitalvideo/spinningdisk/u2473laser/U2-EYFP-ER-100x-1s.html [9] References [1] Agellon, L. (2007), "Lipid Metabolism and the Endoplasmic Reticulum", in Michalak, M. (ed.), The Endoplasmic Reticulum: Fundamentals and Role in Disease, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com.abc.cardiff.ac.uk/bio) [Accessed 12th October 2012]
[2] Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P. (2008). Molecular Biology of the Cell. 5th ed. New York: Garland Science.
[3] Cooper, G.M. Hausman, R.E. (2009) The Cell: A Molecular Approach 5th ed. Sinaur Associates: Massachusetts
[4] Csala, M., Bánhegyi, G. and Benedetti, A. (2006). Endoplasmic reticulum: A metabolic compartment. FEBS Letters 580:2160-2165.
[5] Denecke, J. (2001). Plant Endoplasmic Reticulum.eLS. John Wiley & Sons, Ltd.
[6] Denecke, J. (2007), "The Endoplasmic Reticulum in Plants", in Michalak, M. (ed.), The Endoplasmic Reticulum: Fundamentals and Role in Disease, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com.abc.cardiff.ac.uk/bio) [Accessed 12th October 2012]
[7] Ellgaard. L., Helenius .A., (2003). Quality control in the endoplasmic reticulum. Nature Reviews Molecular Cell Biology 4, 181-191
[8] Fawcett, M.D. (1981). The Cell 2nd ed. WB Saunders & Co: Philadelphia
[9] Hamamatsu (2012). Endoplasmic Reticulum in Epithelial Cells [Online].Germany. Available at: http://learn.hamamatsu.com/galleries/digitalvideo/spinningdisk/u2473laser/U2-EYFP-ER-100x-1s.html [Accessed 16 November 2012]

[10] Hu, J., Shibata, Y., Voss, C., Shemesh, T., Li, Z., Coughlin, M., Kozlov, M. M. et al. (2008). Membrane Proteins of the Endoplasmic Reticulum Induce High-Curvature Tubules. Science 319:1247-1250.

[11] Jaffe, L. A. and Terasaki, M. (1994). Structural changes in the endoplasmic reticulum of starfish oocytes during meiotic maturation and fertilization. Developmental Biology 164:579-587.
[12] Karp, G. (2010). Cell Biology. 6th ed. International: John Wiley & Sons, Inc.
[13] Kapetanovich,L.,, Baughman, C., Lee, T.H. (2005) Nm23H2 facilitates coat protein complex II assembly and endoplasmic reticulum export in mammalian cells Molecular Biology of the Cell 16: 835-848

[14] Lavoie, C., Roy, L., Lanoix, J., Taheri, M., Young, R., Thibault, G., Farah, C. A. et al. (2011). Taking organelles apart, putting them back together and creating new ones: Lessons from the endoplasmic reticulum. Progress in Histochemistry and Cytochemistry 46:1-48.
[15] Martin. W. A briefly argued case that mirochondria and plastids are descendants of endosymbionts, but that the nuclear compartment is not. Proceedings of the Royal Society of London B: Biological Sciences 266: 1387-1395; 1999.

[16] Raeymaekers, L. and Larivière, E. (2011). Vesicularization of the endoplasmic reticulum is a fast response to plasma membrane injury. Biochemical and Biophysical Research Communications 414:246-251.
[17] Roberts, B. (thenewboston) (2012). The Endoplasmic Reticulum [Online]. North Carolina. Available at: http://www.youtube.com/user/thenewboston [Accessed: 16 November 2012].
[18] Sitia, R. (2007), "The Endoplasmic Reticulum as a Most Efficient Antibody Factory", in Michalak, M. (ed.), The Endoplasmic Reticulum: Fundamentals and Role in Disease, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (onlineathttp://hstalks.com.abc.cardiff.ac.uk/bio) [ Accessed 12th October 2012]

[19] Sampathrajan, S. K. (bimatiksblog) (2009). Protein Secretion [Online] India. Available at [Accessed 16 November 2012].

[20] Terasaki, M. and Jaffe, L. A. (1991). Organization of the sea urchin egg endoplasmic reticulum and its reorganization at fertilization. The Journal of Cell Biology 114:929-940.
Terasaki, M., Slater, N. T., Fein, A., Schmidek, A. and Reese, T. S. (1994). Continuous network of endoplasmic reticulum in cerebellar Purkinje neurons. Proceedings of the National Academy of Sciences 91:7510-7514.

[21] Voeltz, G. K., Rolls, M. M. and Rapoport, T. A. (2002). Structural organization of the endoplasmic reticulum. EMBO Rep 3:944-950

[22] Yan M, Li J, Sha B. (2011). Structural analysis of the Sil1-Bip complex reveals the mechanism for Sil1 to function as a nucleotide-exchange factor.Biochemistry Journal 438:447-455 Inspired to learn more?
Click here for a more advanced talk on tertiary structure formation [16]:
http://hstalks.com/main/view_talk.php?t=92&r=17&c=252 Inspired to learn more?
Click here for a more advanced talk on lipid metabolism [1]:
http://hstalks.com/main/view_talk.php?t=96&r=17&c=252 Inspired to learn more?
Click here for a more advanced talk on the role of the ER in plants:
http://hstalks.com/main/view_talk.php?t=100&r=17 Inspired to learn more?
Click here for a more advanced talk on translocation of polypeptides [17]:
http://hstalks.com/main/view_talk.php?t=97&r=17&c=252 [1] Agellon, L. (2007), "Lipid Metabolism and the Endoplasmic Reticulum", in Michalak, M. (ed.), The Endoplasmic Reticulum: Fundamentals and Role in Disease, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com.abc.cardiff.ac.uk/bio) [Accessed 12th October 2012]

[2] Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P. (2008). Molecular Biology of the Cell. 5th ed. New York: Garland Science.

[3] Cooper, G.M. Hausman, R.E. (2009) The Cell: A Molecular Approach 5th ed. Sinaur Associates: Massachusetts

[4] Csala, M., Bánhegyi, G. and Benedetti, A. (2006). Endoplasmic reticulum: A metabolic compartment. FEBS Letters 580:2160-2165.

[5] Denecke, J. (2001). Plant Endoplasmic Reticulum.eLS. John Wiley & Sons, Ltd.

[6] Denecke, J. (2007), "The Endoplasmic Reticulum in Plants", in Michalak, M. (ed.), The Endoplasmic Reticulum: Fundamentals and Role in Disease, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com.abc.cardiff.ac.uk/bio) [Accessed 12th October 2012]

[7] Ellgaard. L., Helenius .A., (2003). Quality control in the endoplasmic reticulum. Nature Reviews Molecular Cell Biology 4, 181-191

[8] Fawcett, M.D. (1981). The Cell 2nd ed. WB Saunders & Co: Philadelphia

[9] Hamamatsu (2012). Endoplasmic Reticulum in Epithelial Cells [Online].Germany. Available at: http://learn.hamamatsu.com/galleries/digitalvideo/spinningdisk/u2473laser/U2-EYFP-ER-100x-1s.html [Accessed 16 November 2012]

[10] Hu, J., Shibata, Y., Voss, C., Shemesh, T., Li, Z., Coughlin, M., Kozlov, M. M. et al. (2008). Membrane Proteins of the Endoplasmic Reticulum Induce High-Curvature Tubules. Science 319:1247-1250.

[11] Jaffe, L. A. and Terasaki, M. (1994). Structural changes in the endoplasmic reticulum of starfish oocytes during meiotic maturation and fertilization. Developmental Biology 164:579-587.

[12] Karp, G. (2010). Cell Biology. 6th ed. International: John Wiley & Sons, Inc. [13] Kapetanovich,L.,, Baughman, C., Lee, T.H. (2005) Nm23H2 facilitates coat protein complex II assembly and endoplasmic reticulum export in mammalian cells Molecular Biology of the Cell 16: 835-848

[14] Lavoie, C., Roy, L., Lanoix, J., Taheri, M., Young, R., Thibault, G., Farah, C. A. et al. (2011). Taking organelles apart, putting them back together and creating new ones: Lessons from the endoplasmic reticulum. Progress in Histochemistry and Cytochemistry 46:1-48.

[15] Martin. W. A briefly argued case that mirochondria and plastids are descendants of endosymbionts, but that the nuclear compartment is not. Proceedings of the Royal Society of London B: Biological Sciences 266: 1387-1395; 1999.

[16] Michalak, M. (2007), "The Endoplasmic Reticulum: Protein Folding and Control of Calcium Homeostasis", in Michalak, M. (ed.), The Endoplasmic Reticulum: Fundamentals and Role in Disease, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/bio) [Accessed on 12th October 2012]

[17] Nicchitta, C. (2007), "Endoplasmic Reticulum, Protein Synthesis and Translocation Machinery", in Michalak, M. (ed.), The Endoplasmic Reticulum: Fundamentals and Role in Disease, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/bio) [Accessed on 12th October 2012]

[18] Raeymaekers, L. and Larivière, E. (2011). Vesicularization of the endoplasmic reticulum is a fast response to plasma membrane injury. Biochemical and Biophysical Research Communications 414:246-251.

[19] Roberts, B. (thenewboston) (2012). The Endoplasmic Reticulum [Online]. North Carolina. Available at: http://www.youtube.com/user/thenewboston [Accessed: 16 November 2012].

[20] Sitia, R. (2007), "The Endoplasmic Reticulum as a Most Efficient Antibody Factory", in Michalak, M. (ed.), The Endoplasmic Reticulum: Fundamentals and Role in Disease, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (onlineathttp://hstalks.com.abc.cardiff.ac.uk/bio) [ Accessed 12th October 2012]

[21] Sampathrajan, S. K. (bimatiksblog) (2009). Protein Secretion [Online] India. Available at [Accessed 16 November 2012].

[22] Terasaki, M. and Jaffe, L. A. (1991). Organization of the sea urchin egg endoplasmic reticulum and its reorganization at fertilization. The Journal of Cell Biology 114:929-940.
Terasaki, M., Slater, N. T., Fein, A., Schmidek, A. and Reese, T. S. (1994). Continuous network of endoplasmic reticulum in cerebellar Purkinje neurons. Proceedings of the National Academy of Sciences 91:7510-7514.

[23] Voeltz, G. K., Rolls, M. M. and Rapoport, T. A. (2002). Structural organization of the endoplasmic reticulum. EMBO Rep 3:944-950

[24] Yan M, Li J, Sha B. (2011). Structural analysis of the Sil1-Bip complex reveals the mechanism for Sil1 to function as a nucleotide-exchange factor.Biochemistry Journal 438:447-455 References [8] [24] [21] [7] The Structure & Function
of the Rough and
Smooth Endoplasmic
Reticulum http://bit.ly/14uL0LR Test yourself! Figure 5. An electron micrograph of the rough endoplasmic reticulum. Figure 6. The 3D structure of BiP Figure 8. The ER enzyme Glucosidase II is responsible for the dissociation of the glycoprotein substrate from calnexin or caltreculin. This is achieved through hydrolysing the glucose of the monoglucosylated core glycan. On their release, correctly folded glycoproteins can exit the ER. By contrast, non-native glycoproteins are substrates for the UDP-glucose:glycoprotein glucosyltransferase, which places a single glucose back on the glycan, thereby promoting a renewed association with calnexin and calreticulin.

If the protein is permanently misfolded, the mannose residue in the middle branch of the oligosaccharide is removed by alpha 1,2-mannosidase I. This leads to recognition by the ER degradation-enhancing 1,2-mannosidase-like protein (EDEM), which probably targets glycoproteins for ER-associated degradation (ERAD) [7]. Figure 9. A table comparing the features of the rough and smooth endoplasmic reticulum. Figure 7: A basic overview of the Ubiquitin Proteasome System, showing the use of lysosomes to degrade the mis-folded protein. How to use this learning resource: For an overview of the entirety of the endoplasmic reticulum, follow the pre-programmed pathway of the Prezi.
Where you see this symbol: Follow the yellow lines for additional information of the subject. Contents Introduction: 4
The Smooth ER: 8
The Rough ER: 14
Comparison of the Rough and Smooth ER: 28
Origins of the Endoplasmic Reticulum: 30
Interactive Quiz: 32
References: 33 Self-Directed Learning Question Compare and contrast the rough and the smooth endoplasmic reticulum. Self-Directed Learning Questions Describe, using text and figures, the secretory pathway. Figure 2. An artist's representation of the structure of the smooth ER. Figure 4. An artist's impression of the structure of the rough ER. Image taken from BI2202 lecture notes. Image taken from BI2202 lecture notes. Describe, using specific examples, the fate of proteins in the ubiquitin proteasome pathway.
See the full transcript