Endoplasmic Reticulum

The endoplasmic reticulum (ER) is a series of interconnected membranes or flattened sacs adjacent and connected to the nuclear membrane. The ER comes in two different morphological forms: smooth endoplasmic reticulum (sER) and rough endoplasmic reticulum (rER). The primary function of the sER is to serve as a platform for the synthesis of lipids (fats), carbohydrate (sugars) metabolism , and the detoxification of drugs and other toxins.

Tissues and organs that directly participate in these activities, such as the liver, are enriched in sER. Morphologically, the rER is studded with ribosomes that participate in protein synthesis giving its "rough" appearance when viewed with the electron microscope. The proteins synthesized on the ER are transported from the ER membranes by small vesicles that pinch off the surface and enter the Golgi membrane stack (cisternae). From the Golgi, the proteins are transported to the cell surface or to other organelles .

The Rough Endoplasmic Reticulum (rER)

The rER is a series of stacked membranes closest to the nucleus that is the site for synthesis and maturation of proteins destined for the plasma membrane, secretory vesicles, or endocytic vesicles. Many ribosomes stud the cytoplasmic face of the rER, as well as populating the surrounding cytoplasm. Messenger ribonucleic acid (mRNA) transcribed in the nucleus leaves the nucleus via the nuclear pores and is transported into the cytoplasm. Docking sites on the head or "N-terminus" of the mRNA allow the ribosome to bind to it and initiate translation , decoding the linear sequences of bases in the RNA to an amino acid sequence that will constitute a protein.

Translocation into the Lumen. The first segment of the growing peptide consists of a "signal sequence" that binds to a pre-existing signal recognition particle (SRP) from the cytoplasm. The SRP is a small protein/RNA complex that acts as a targeting guide and is essential for protein translocation into the rER lumen (interior chamber). The cytoplasmic surface of the rER contains a protein called the SRP receptor that binds to the SRP, anchoring the ribosome with its growing peptide to the rER membrane. As translation proceeds, the peptide is fed into the lumen of the rER where the signal sequence is cut off and additional changes called post-translational modifications proceed immediately.

Glycosylation. Proteins are modified by the addition of carbohydrates (glycosylation) to specific amino acids in the peptide chain. One of the most common modifications is to attach an oligosaccharide (oligo means "few"; saccharide means "sugar" or "carbohydrate") to the growing peptide. The branched oligosaccharide is composed of a combination of three sugars: glucose, mannose, and N-acetylglucosamine that can be further modified in the rER and, later, in the Golgi complex. The oligosaccharide modifications on proteins assist in the correct folding of the protein and help stabilize it. The oligosaccharide may also assist in targeting the protein to the correct location in the cell.

Protein Folding. The ER lumen maintains a chemical environment that ensures that proteins are folded into the correct conformation . Misfolded proteins are useless and may cause problems if they are detected as "foreign structures" by the immune system of the body. How does the ER ensure that proteins are folded correctly? Newly synthesized proteins are quickly associated with ER "chaperone proteins" and folding enzymes that assist in the folding of the proteins into their correct conformations. A protein that is misfolded is retained by the ER and degraded. It is not known exactly how the ER recognizes misfolded proteins, but it may be able to recognize specific domains or segments on the proteins. For example, a hydrophobic domain (water-avoiding segment) should be tucked away inside the protein, but a misfolded protein may have this domain protruding outward. Such a protein would be retained and degraded.

Smooth Endoplasmic Reticulum (sER)

Lipid synthesis takes place at the interface of the sER membrane and the cytosol . The initial starting material is embedded in the membrane while cytosolic enzymes and building materials continually modify it until the lipid product is complete. How do these lipids, which are made in the sER, get to the plasma membrane or other organelle membranes? There are two models. According to the membrane budding model, a patch of membrane pinches off the ER and forms a vesicle that finds its way to its destination. In the phospholipid exchange model, water-soluble proteins remove the lipid from the ER membrane and release it into the target membrane.

The ER is also involved in cell signaling by releasing stored calcium ions (Ca²⁺ ) into the cytosol. This serves to amplify signals from molecules in very low concentrations, such as extracellular hormones , thus triggering a response in cells. Without amplification of the initial signal, the cells will not respond to the hormone. The chain of events can be summarized as follows: (1) a hormone binds to a specific receptor on the plasma membrane; (2) the receptor interacts with several other membrane-bound signaling proteins to produce a molecule called inositol 1,4,5-trisphosphate (IP₃), which is released into the cytoplasm; and (3) IP₃ interacts with its own receptor on the ER membrane and passes the signal on to a Ca²⁺ pump. Once the pump is activated, it releases a massive amount of calcium from the ER lumen into the cytoplasm. The Ca²⁺ ions act as "second messengers" that turn on several cellular systems ranging from cell motility to protein synthesis.

see also Golgi; Lipids; Nuclear Transport; Nucleus; Protein Synthesis; Ribosome Signaling and Signal Transduction

Edward Harris and James Cardelli

Bibliography

Ellgaard, Lars, et al. "Setting the Standard: Quality Control in the Secretory Pathway." Science 286 (December 3, 1999): 1882–1887.

Lodish, Harvey F., et al. Molecular Cell Biology, 4th ed. New York: W. H. Freeman and Co., 2000.

Putney, James W., Jr. "'Kissin' Cousins': Intimate Plasma Membrane-ER Interactions Underlie Capacitative Calcium Entry." Cell 99 (1999): 5–8.

Endoplasmic Reticulum

Endoplasmic reticulum is a network of membranes or tubes in a cell through which materials move. As an organelle in a eukaryotic cell (complex cells having nuclei and other organelles), it is involved with the production of new proteins as well as with the movement of materials throughout the cell.

The name endoplasmic reticulum means "an inside formed network," and these words properly describe this network of connected folds, tubes, and sacs that are found in all eukaryotic cells (those with a distinct nucleus). As an organelle in a cell, the endoplasmic reticulum is a specialized structure and has certain tasks to perform. The endoplasmic reticulum has been described as the pipeline or conveyer belt through which supplies are moved about the factory (or the cell). Viewed through a microscope, the endoplasmic reticulum looks like flat, tubular membranes that are connected to the nucleus and which spread throughout the interior of the cell. There are two types of endoplasmic reticulum: rough endoplasmic reticulum and smooth endoplasmic reticulum. Rough endoplasmic reticulum appears to have a pockmarked, or rough outer surface, and this is because it is covered with ribosomes, which are structures in the cell that make proteins. Smooth endoplasmic reticulum has no ribosomes dotting its surface. Smooth endoplasmic reticulum has the job of packaging and distributing materials needed for making proteins and other substances, and also is responsible for "detoxifying" any substance in the cell that might be poisonous. Both types of endoplasmic reticulum are essential to the cell if it is to be able to move materials around to where they are needed. There is always a large amount of endoplasmic reticulum within a cell, and in many cells it takes up nearly half the amount of interior space. Although both are involved with transport, smooth endoplasmic reticulum curves around the cell's cytoplasm (its jelly-like fluid) like interconnecting pipelines, while rough endoplasmic reticulum looks more like stacked and flattened sacs. Both smooth and rough endoplasmic reticulum are connected directly to many other organelles in the cell, and without the membrane pipeline that the endoplasmic reticulum provides, eukaryotic cells would not be able to carry out many of their functions.

[See alsoCell; Organelle ]

endoplasmic reticulum (ER) A system of membranes within the cytoplasm of plant and animal cells. It forms a link between the cell and nuclear membranes (see cisterna) and is the site of protein synthesis. It is also concerned with the transport of proteins and lipids within the cell. Rough ER has ribosomes attached to its surface; proteins synthesized on the ribosomes are enclosed in vesicles and transported to the Golgi apparatus. Smooth ER lacks ribosomes; it is the site of important metabolic reactions, including phospholipid and fatty-acid synthesis.

endoplasmic reticulum (ER) Network of membranes and channels in the cytoplasm of eukaryote cells. It helps to transport material, such as proteins, inside the cell. Minute granules called ribosomes, consisting of protein and a form of ribonucleic acid (RNA), cover parts of the endoplasmic reticulum.

endoplasmic reticulum A complex network of cytoplasmic (see CYTOPLASM) membranaceous sacs and tubules which appears to be continuous with both the nuclear and plasma membranes. It occurs in two forms: that bearing ribosomes is called rough ER; that without, smooth ER. Both are involved in the synthesis, transport, and storage of cell products.