Rough Endoplasmic Reticulum

Rough Endoplasmic Reticulum

The rough endoplasmic reticulum (ER rough) is part of the cell’s endomembrane system and a subset of the endoplasmic reticulum (ER). This organelle is mainly concerned with the synthesis, folding, and modification of proteins, especially those that have to be delivered to different organelles within the cell or secreted by the cell. The rough ER is also involved in the cell’s response to unfolded proteins and plays a role in the induction of apoptosis due to its close interaction with mitochondria.

Rough ER is characterized by the presence of membrane-bound ribosomes, which give it a distinctive appearance under the microscope. These ribosomes look like studs and distinguish the organelle from the smooth sections of the ER. Some proteins are also synthesized from ribosome chains called polysomes. The rough ER can also be identified by its morphology: it often consists of tortuous, flattened sac-like structures that arise near the nucleus. The lumen of the rough ER is adjacent to the perinuclear space and the membranes of the rough ER are connected to the outer nuclear membrane.

Structure of the Rough Endoplasmic Reticulum

The emergency room can be morphologically divided into two structures: cisterns and leaves. The rough endoplasmic reticulum consists primarily of leaves, a two-dimensional array of flattened sacs that run the length of the cytoplasm. In addition to ribosomes, these membranes contain an important protein complex called a translocon, which is necessary for protein translation in the rough ER.

The structure of the rough ER is also closely related to the presence of cytoskeletal elements, particularly microtubules. If the microtubule structure is temporarily disrupted, the ER network collapses and only re-forms after the cytoskeleton has been rebuilt. Changes in the microtubule polymerization pattern are also reflected in changes in ER morphology. Furthermore, when ribosomes separate from the rough endoplasmic reticulum layers, these structures can disintegrate and form tubular cisterns.

The edges of the ER panels have a strong curvature that must be stabilized. Proteins are known as reticules and DP1 / Yop1p play an important role in this stabilization. These proteins are integral membrane proteins that form oligomers to form the lipid bilayer. In addition, they also use a structural motif that is inserted into a membrane sail and reinforces its curvature. These two classes of proteins are superfluous because the overexpression of one protein seems to compensate for the lack of the other protein.

Functions of the Rough Endoplasmic Reticulum

The rough endoplasmic reticulum performs a number of functions within the cell, largely associated with protein synthesis. Polypeptides are synthesized, modified, folded into their correct three-dimensional shape, and classified into an organelle or marked for secretion. It also plays an important role in modulating the response of cells to stress and in quality control for correct protein folding. When the number of unfolded proteins increases, cells alter their tubule: lamina ratio. This could arise from the increased area available within the sheets of the rough ER to rescue the unfolded protein or it could reflect the need for the distinctive rough ER proteome.

The rough ER proteome reflects its specific role within the cell. It contains enzymes involved in RNA metabolism that bind and modify RNA. This is necessary since the organelle is involved in the translation of RNA into protein. It also contains proteins that recognize various signal sequences within a growing polypeptide and aid in its translocation. The glycosylation enzymes and proteins that act as molecular chaperones that ensure proper folding of the synthesized polypeptides are also important proteins within this organelle. Occasionally, ER induces apoptosis in response to excess protein deployed within the cell. This function is mediated in consort with the mitochondria.

Protein Synthesis

Translation of all proteins begins in the cytoplasm after a processed mRNA transcript has been exported from the nucleus. Translation begins with the binding of a ribosome to a mature mRNA transcript. However, after the first amino acids have been generated, some polypeptides will be imported into the ER before translation can continue. This relies on the recognition of a short stretch of amino acids, also known as a signal sequence, by abundant cytosolic ribonucleoproteins called signal recognition particles (SRP). The SRP link temporarily stops translation and allows the entire translation machinery to move to the ER. In the ER, the resulting polypeptide is introduced into the organelle through transmembrane channels called translocons. These channels consist of a complex of proteins that allow the polypeptide to cross the hydrophobic lipid bilayer of the ER membrane. The channel is not very wide and therefore requires the insertion of the polypeptide as an unfolded chain of amino acids. At this point, the SRPs dissociate from the polypeptide and translation resumes. After the first amino acids enter the light, ER-resident enzymes often break the signal sequence. Newer amino acids are added to the growing polypeptide chain as the ribosome remains attached to the ER membrane and the resulting protein continues to insert into the ER lumen. This process is known as a co-translational import into the ER.

The process of translation of membrane-bound ribosomes is particularly important for the proteins to be secreted. Thus, the rough ER is prominently represented in liver cells that secrete serum albumin, cells of the digestive system that secrete enzymes, endocrine cells that synthesize and secrete protein hormones (such as insulin), and in cells that they form the proteins of the extracellular matrix. . Rough ER protein synthesis is also important for membrane-bound proteins, especially those such as G-protein-coupled receptors (GPCRs), which contain multiple hydrophobic segments and cross the membrane more than once by hairpin bends in their structure. The precise role of ER-resident proteins and translocons in coping with the complex task of translating these proteins is not fully understood.

In mammalian breasts, the secretory system with the rough ER is crucial during lactation. The individual layers of rectangular epithelial cells are involved in the main milk production process. The nucleus of these cells is located at the basal end of the cell and the rough ER apparatus and Golgi apparatus are close to the nucleus. The proteins synthesized by crude ER include the most prominent milk protein, casein, and whey proteins. These proteins pack into secretory vesicles or large micelles and migrate through the Golgi network before fusing with the plasma membrane and releasing their contents into the milk ducts.

Protein Folding and Quality Control

One of the side effects of translation in rough ER, in which the polypeptide is translocated as an unfolded chain of amino acids, is that these short stretches must be protected until they can form their final 3D structure so that they do not aggregate prematurely. An important mechanism to ensure correct protein folding is the glycosylation of the resulting polypeptide by enzymes called oligosaccharide transferases. These enzymes are part of the rough ER membrane translocon complex. Glycosylation increases the solubility of peptide chains and protects them until molecular chaperones can bind to them and facilitate their folding. The prominent molecular companions of rough ER are immunoglobulin-binding protein (BiP), calnexin (CNX), and calreticulin (CRT). CNX / CRT supports protein folding in relation to glycosylation. BiP contains a substrate-binding region that recognizes hydrophobic sections in the polypeptide and an ATPase domain that increases its affinity for these sections. Members of the DnaJ / Hsp40 protein family support BiP in its task by modulating its ATPase activity and enhancing its interaction with nucleotide exchange factors. ER also contains enzymes that catalyze the formation of disulfide bridges and chaperones and specific substrate enzymes that are necessary for certain proteins. It also maintains an oxidative environment to aid in this task.

BiP, CNX / CRT, and other chaperones accumulate in regions of the ER that interact closely with mitochondria. This section of the emergency room is called the MAM, or Mitochondria-Associated Membrane. The MAM is becoming an important signaling center within the cell, integrating signals from the ER and playing a role in calcium homeostasis, autophagy, apoptosis, and mitochondrial function.

Despite these mechanisms to ensure that proteins are correctly folded, some must be removed from the system, either due to translation errors or genetic mutations that lead to the production of defective proteins. This is accomplished through quality control systems within the ER, which “check” the newly synthesized proteins. If the polypeptide does not fold in its native state, the molecular chaperones reattach the polypeptide and make another attempt to fold the protein into its correct form. If repeated attempts fail, misfolded proteins can be exported to the cytosol and removed by ubiquitin-mediated protein degradation by the proteasome.

Protein Sorting

Once the proteins are synthesized and folded, they must be transported to their final destination. The first step in this process is the formation of vesicles from the edges of the rough ER. These vesicles carry cargo into the Golgi network and are created by the coordinated action of a variety of proteins, beginning with the vesicular coat protein complex II (COPII). For COPII to perform its functions, a GTPase enzyme and a nucleotide exchange factor are required. Together, these proteins distort the membrane and allow the formation of a vesicle that carries an appropriate charge. Proteins that need to remain in the ER are returned from the Golgi by retrograde transport, using vesicles produced by a related protein called COPI.

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Rough Endoplasmic Reticulum

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