Rough endoplasmic reticulum
plural: rough endoplasmic reticula
Endoplasmic reticulum is one of the most prominent organelles of a eukaryotic cell. The endoplasmic reticulum (ER) is an organelle that occurs as interconnected network of flattened sacs or tubules (called cisternae) in the cytoplasm. The membranes of the ER are connected to the outer nuclear envelope. They may also extend into the cell membrane. There are two kinds of ER: the rER, or the rough endoplasmic reticulum, and the sER, or the smooth endoplasmic reticulum.
The rER is bears many ribosomes on its outer surface giving it a rough appearance as seen under the microscope; hence, the name. The presence of ribosomes on rER is an indication that the latter is involved in protein synthesis and secretion. The organelle synthesizes and secretes serum proteins (such as albumin) in the liver, and hormones (such as insulin) and other substances (such as milk) in the glands. Nevertheless, the ribosomes that give the endoplasmic reticulum a 'rough' appearance are not always bound to the ER. They bind to it when it starts to synthesize membrane-bound proteins destined for sorting. A cue is a particular protein-nucleic acid complex that forms in the cytosol.
The rER has a translocon, i.e. a multiprotein complex involved in the translocation of nascent polypeptides, and in this case, from the cytosol to the interior of the rER across the rER membranes. The translocon serves as the binding site where ribosome can dock to the endoplasmic reticulum. The bound ribosomes, though, are attached to the ER transiently. They may come and go. They attach to the endoplasmic reticulum (via the translocon) when a signal peptide is synthesized (i.e. by protein translation at the ribosome) and then recognized by a signal recognition particle.
Since rER has ribosomes attached to its surface it is therefore involved in protein synthesis and protein folding, as well as the shuttling of proteins to the Golgi apparatus where the nascent protein undergoes maturation. It synthesizes and secretes serum proteins (such as albumin) in the liver, and hormones (such as insulin) and other substances (such as milk) in the glands. The rER is also involved in the manufacture of lysosomal enzymes (in which a marker, mannose-6-phosphate, is later added in the Golgi apparatus). It is also where certain integral membrane proteins are formed. N-linked glycosylation also occurs here (O-glycosylation occurs in the Golgi).
Common biological reactions
Protein synthesis and secretion
Protein synthesis is a process of creating protein molecules. In biological systems, the major steps are amino acid synthesis, transcription and translation. Transcription is a nuclear event wherein mRNA template, encoding the sequence of the protein in the form of a trinucleotide code, is transcribed from DNA to provide a template for translation. Translation is a cytoplasmic process and the site of translation is the ribosomes. There, the amino acids are added by tRNAs and then are linked together in a specific order as specified in the mRNA transcript. Subsequent to these events are maturation processes, such as proteolysis, post-translational modification, and protein folding. In the early phase of translation, a signal peptide is synthesized (i.e. by protein translation at the ribosome). The signal is an indication that the protein is for further processing in the ER. When this signal is recognized by a signal recognition particle the ribosome translating the protein docks to the endoplasmic reticulum via the translocon. The ribosome, then, returns back to the translation of the protein. The chain continues to grow as the mRNA transcript is translated through the docked ribosome. The chain eventually makes its way into the ER through the translocon that spans across the ER membranes. The signal peptide is removed by a signal peptidase in the lumen of the ER. The nascent protein is folded in the ER by the chaperone proteins (e.g. ERp29, protein disulfide isomerase, BiP/Grp78, calnexin, etc.). The properly-folded protein is then packed into a transport vesicle to be shuttled to the Golgi apparatus where it would undergo maturation for transport along the cytoskeleton to other cytoplasmic organelles like lysosomes and peroxisomes or for secretion out of the cell. Some of the proteins synthesized inside the ER will be retained, such as those that become part of the ER membrane. Those that are retained in the ER have a retention motif, e.g. KDEL (for proteins retained in the ER lumen) and KKXX (for transmembrane proteins in the ER membrane).
ER stress response
An unfolded or misfolded protein triggers an endoplasmic reticulum stress response. This happens when certain disturbances occur, such as disturbances in the redox regulation, calcium regulation, viral infection, and glucose deprivation. A distinctive feature of a misfolded protein is the lack of glucose residues, which are attached via N-linked glycosylation. The initial response is for glycosylation by the enzyme UGGT (UDP-glucose:glycoprotein glucosyltransferase). A heat shock protein glucose regulate protein 78 may bind to the hydrophobic residues of the misfolded protein to prevent its transit. If protein misfolding continues, the protein is headed towards degradation to prevent it from aggregating with other misfolded proteins. By endoplasmic reticulum-association degradation (ERAD), the ERAD chaperone shuttles the misfolded protein to the cytosol for degradation by cytosolic proteasomes (via the ubiquitin-proteasome pathway). If these measures fail to restore the normal function of the cell within a certain period of time, the next response is geared towards apoptosis.
- granular endoplasmic reticulum
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