Reticular network of membranes within cytoplasm is called endoplasmic reticulum (ER). The labyrinthine network of ER pervades the entire cytoplasmic fluid and provides continuous but a dynamic compartmentalization and fluidity. In fact plasma membrane and nuclear membrane are interconnected through various forms of endoplasmic reticulum.
Endoplasmic Reticulum exhibits various forms and shapes. They also show variations in their chemical composition and structural organization. Some of the ER membranes are found as flat membranous sheets and some are in the form of branched tubular structures. They also exist as membranes vesicles. Nevertheless such forms are not constant and they undergo rapid changes from one from to another form and vice versa.
Though ER, is basically made up of two unit membranes containing lumen in between which, is filled with fluid. The extent and magnitude of ramification of this membrane system varies from cell type to cell type. The cell that is actively engaged in protein synthesis and metabolically active contains greater amount of ER occupying more than ¾ th of the cytoplasmic space.
Endoplasmic membranes are further classified into rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER). The former is studded with a large number of ribosomes on its cytosolic surface. The bound ribosomes are active in protein synthesis; on the contrary, SER is free from ribosomes. In RER, ribosomes are bound to the membrane surface by its larger subunit. The binding is attributed to the presence of two specific transmembrane proteins called ribophorins of mol wt. 65 KD and 63 KD respectively. These proteins are absent in SER. Most of the ribosomes found on RER membranes are in the form of polysome complexes actively engaged in protein synthesis. The nascent polypeptides thus synthesized enter into the lumen by its NH3 end through a groove found in the large ribosomal subunit. The first 20-40 amino acid recidues found at the NH2 end of the polypeptide chain act as signal polypeptides and they facilitate the translocation of proteins into the lumen of the RER. The proteins thus packed into RER lumen are transported towards SER to reach specific destinations. Some of the ER membranes carrying proteins either reach Golgi bodies or pinch off into vesicles which ultimately find their way into respective organelles. The ER membranes are supported by microtubular cytoskeleton structures. That is the reason they remain intact and also mobile. At the time of cell division at end of prophase MTs undergo depolymerization, with that ER collapse into fine vesicles. They reappear at the return of telophase, and MTs help in organizing the membranes.
Endoplasmic reticular membranes contain high lipid content in relation to its protein partners. The common lipids found are phospholipids, phosphotidyl inositol, neutral lipids, sulfolipids, cholesterol and some phytosterols. Nearly 30-40 different types of ER membrane proteins have been isolated, of which many are enzymes like cytochrome P 450 and its subgroups, electron transport protein complexes like Cytochrome C reductase, Cytochrome b5 reductase. Gulcose 6 phosphotases are also common in ER. Furthermore, though ER shows similarity in their structural appearances they exhibit chemical heterogeneity at their cytoplasmic and lumen surfaces. They do contain a variety of resident proteins, which perform functions like, protein folding, protein modification and protein transport.
There are many views with regard to the biosynthesis of endomenbranes. According to one view, the membranes develop from plasma membranes. According to one view, the membranes develop from plasma membranes by inward invagination and growth. But other view points out that ER develop from the outer nuclear membrane. Both these views point out that ER develops from both plasma membranes and outer nuclear membrane. It is also true that both plasma membranes and nuclear membrane are also derived from endomenbranes. In protein synthesis and other cell membrane components are involved in the synthesis of various liquid components, thus they get self assembled by incorporating required proteins and lipid and other fatty acid derivatives.
Endoplasmic membranes found in the cytoplasmic fluid are highly dynamic and show rapid but sweeping movements. In fact they exhibit high fluidity because the membranes are always in constant vesiculation and rejoining with other vesicles. Some of the important functions of it are listed below RER is engaged in the synthesis of a wide variety of proteins at different site. SER is involved in glycogenolysis. In plant cells SER is responsible for the secretion of vesicles containing raw materials for cell wall formation. SER is also responsible for the synthesis of various kinds of lipids and its derivatives. ER enzymes like Cyt. P450 and its allied enzymes are capable of detoxification of drugs. Alcohols and other metabolically harmful components are detoxified; but the same can also cause damage to the liver.
Density of ER in cytoplasm.
Rough and smooth ER; http://thecellorganelles.weebly.com/
The endoplasmic reticulum manufactures, processes, and transports a wide variety of biochemical compounds for use inside and outside of the cell. Consequently, many of the proteins found in the cisternal space of the endoplasmic reticulum lumen are there only transiently as they pass on their way to other locations. Other proteins, however, are targeted to constantly remain in the lumen and are known as endoplasmic reticulum resident proteins. These special proteins, which are necessary for the endoplasmic reticulum to carry out its normal functions, contain a specialized retention signal consisting of a specific sequence of amino acids that enables them to be retained by the organelle. An example of an important endoplasmic reticulum resident protein is the chaperone protein known as BiP (formally: the chaperone immunoglobulin-binding protein), which identifies other proteins that have been improperly built or processed and keeps them from being sent to their final destinations. http://micro.magnet.fsu.edu/
ER and mitochondrial associated reactive oxygen species (ROS) production under ER stress. ROS are generated in the ER as a part of an oxidative folding process during electron transfer between protein disulfide Isomerase (PDI) and endoplasmic reticulum oxidoreductin-1 (ERO-1). ER-induced oxidative stress is further tuned for the generation of mitochondrial ROS. Ca2+ ions released from the ER augments the production of mitochondrial ROS which induces the Kreb’s cycle to further induce oxidative phosphorylation at the electron transport chain (ETC). Moreover, Ca2+ ions increase cytochrome c release impairing electron transfer, altering mitochondrial membrane potential and increasing the generation of ROS. http://www.mdpi.com/
Retrogade transport from Golgi to ER: www.studyblue.com
Unfolded proteins are transported out of ER into cytosol where they are degraded.
Proteins (bad) transported back into cytosol for degradation; http://www.scs.illinois.edu/
Certain proteins from cis golgi are retrived back to ER via signal recognition sequences; http://quizlet.com/
1. Luminal proteins: Proteins found in the lumen of the Golgi complex that need to be transported to the lumen of the ER contain the signal peptide KDEL. This sequence is recognized by a membrane-bound KDEL receptor. In yeast, this is Erd2p and in mammals it is KDELR. This receptor then binds to an ARF-GEF, a class of guanine nucleotide exchange factors. This protein in turn binds to the ARF. This interaction causes ARF to exchange its bound GDP for GTP. Once this exchange is made ARF binds to the cytosolic side of the cis-Golgi membrane.
2. Membrane proteins: Transmembrane proteins which reside in the ER contain sorting signals in their cytosolic tails which direct the protein to exit the Golgi and return to the ER. These sorting signals, or motifs, typically contain the amino acid sequence KKXX, which interact with COPI. The order in which adaptor proteins associate with cargo, or adaptor proteins associate with ARFs is unclear, however, in order to form a mature transport carrier coat protein, adaptor, cargo, and ARF must all associate.
Network of ER
Ribosomes bound to ER; http://jennarever.weebly.com/
Rough ER for they are bond by translational ribosomes.www.doctorate.com
ER with MAMs:
ER with Mitochondrial Membranes (MAMs)
Chronichepatites C causes metabolic disorders lead to cancer decvelopement. Many lines of evidence suggest that mitochondrial dysfunctions, including modification of metabolic fluxes, generation and elimination of oxidative stress, Ca2+ signaling and apoptosis, play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitrostudies performed so far have shown that several of the hepatitis C virus (HCV) proteins localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory, probably due to the use of artificial expression and replication systems.The ER is the major site ofr storage of Ca2+.Alteration in oxidative environmenrt in ERand also intra ER Ca2+ results ER stress induced reactive Oxygen (RoS) ;www.mdpi.com
Hypothetical models of the role of contacts between mitochondria and ER in apoptosis. The hFis1/Bap31 platform transmits the mitochondrial stress signal to the ER via the activation of procaspase-8. The cytosolic region of the ER integral membrane protein Bap31 is cleaved by activated caspase-8 to generate proapoptotic p20Bap31, which causes rapid transmission of ER calcium signals to the mitochondria via the IP3 receptor. At close ER-mitochondria contact sites, mitochondria takes up calcium into the matrix via the mitochondrial calcium channels MICU1 or LETM1. The massive influx of calcium leads to mitochondrial fission, cristae remodeling, and cytochrome release. Mfn2 is enriched in the mitochondria-associated membranes (MAM) of the endoplasmic reticulum (ER), where it interacts with Mfn1 and Mfn2 on the mitochondria to form interorganellar bridges. Upon apoptosis signal, a BH3-only member of the Bcl-2 family, Bik, induces Ca2+ release from the ER and, in turn, induces Drp1 recruitment to the mitochondria and their fragmentation and cristae remodeling. SERCA, sarco/endoplasmic reticulum Ca2+-ATPase. MICU1, mitochondrial calcium uptake 1. LETM1, leucine zipper/EF hand-containing transmembrane 1; http://www.hindawi.com/
Mitochondria are cellular organelles involved in host‐cell metabolic processes and the control of programmed cell death. A direct link between mitochondria and innate immune signalling was first highlighted with the identification of MAVS—a crucial adaptor for RIGI‐like receptor signalling—as a mitochondria‐anchored protein. Recently, other innate immune molecules, such as NLRX1, TRAF6, NLRP3 and IRGM have been functionally associated with mitochondria. Furthermore, mitochondrial alarmins—such as mitochondrial DNA and formyl peptides—can be released by damaged mitochondria and trigger inflammation. Therefore, mitochondria emerge as a fundamental hub for innate immune signalling. http://embor.embopress.org/