Endoplasmic Reticulum (ER) and Endomembrane System

• The endoplasmic reticulum (ER) is part of the endomembrane system, which is a group of membranous organelles within eukaryotic cells.
• The endomembrane system includes the ER, Golgi apparatus, endosomes, lysosomes, vacuoles, and nuclear membranes, all working together.
• Processes coordinated by the endomembrane system involve synthesis and maturation of carbohydrates, lipids, and proteins.
• The endomembrane system is involved in sorting, targeting, and packaging synthesized materials.
• The endomembrane system regulates bulk transport, endocytosis, exocytosis, and phagocytosis.
• The endomembrane system plays a role in intracellular digestion and processing.
• Mitochondria, chloroplasts, and peroxisomes are not part of the endomembrane system because their membranes function independently.

RER and SER Structures

• The ER consists of rough ER (RER) and smooth ER (SER), which are structurally and functionally distinct but physically connected.
• Both RER and SER are membranous systems that enclose a lumen, dividing the cytoplasm into the cytosol and the lumen.
• The lumen composition differs from the cytosol.

Rough ER

• RER has interconnected flattened sacs (cisternae) with ribosomes attached to the cytosolic face.
• The RER membrane is continuous with the outer nuclear membrane, which also has ribosomes on its cytosolic face.

Smooth ER

• SER consists of interconnected tubular structures without ribosomes.

SER/RER Ratio

• The amounts of SER and RER vary among cell types.
• Extensive RER is found in cells with active protein synthesis, such as pancreatic cells.
• Extensive SER is found in cells with active steroid synthesis, such as Leydig cells.
• Hepatocytes have similar amounts of RER and SER.

SER Functions

• SER is well-developed in skeletal muscle fibers, where it is called the sarcoplasmic reticulum.
• SER functions include steroid hormone and lipid synthesis, detoxification of xenobiotics, dephosphorylation of glucose 6-phosphate, and sequestering calcium ions.

Synthesis of Steroid Hormones and Lipids

• Steroid hormone synthesis occurs in endocrine cells and requires enzymes present in the SER membrane and lumen.
• Integral proteins in the SER membrane of hepatocytes produce HDL, LDL, and other lipids, such as phospholipids.

Detoxification of Xenobiotics

• Xenobiotics are foreign chemicals not synthesized by the organism.
• Detoxification of toxic substances occurs mainly in the liver, but other organs also contribute.
• Detoxification transforms hydrophobic chemicals into hydrophilic metabolites for elimination in urine or bile.
• Oxygen-transferring enzymes, such as cytochrome P450s in the SER, carry out detoxification.

Dephosphorylation of Glucose 6-Phosphate

• Hepatocytes store glucose as glycogen granules next to the SER.
• Low glycemia triggers the conversion of glycogen back into glucose.
• Glycogen is converted to glucose 6-phosphate, which remains in the cytoplasm.
• The SER membrane contains glucose 6-phosphatase, which dephosphorylates glucose 6-phosphate into glucose.
• Glucose is then transported out of the cell.

Sequestering Calcium Ions

• SER collects calcium ions inside the lumen and releases them upon stimulation.
• Calcium is collected via calcium-binding proteins within the SER.
• Regulated calcium release from the SER triggers muscle contraction.

RER Functions

• RER functions include protein synthesis by membrane-bound ribosomes, glycosylation of proteins, lipid biosynthesis and membrane proliferation, and export of vesicles to the Golgi apparatus.

Synthesis of Proteins by Membrane-Bound Ribosomes

• RER is the site of protein synthesis due to attached ribosomes.
• Secreted proteins and proteins of the endomembrane system are synthesized by these ribosomes.
• Other proteins are synthesized by free ribosomes.
• Proteins are exported to specific compartments after translation (post-translational delivery) based on their signal sequences.

Mechanism of Attachment and Polypeptide Insertion

• A signal sequence mediates protein attachment using the signal recognition particle (SRP).
• The translocon channel inserts the growing polypeptide into the RER lumen.
• The signal sequence is removed by signal peptidases.
• The SRP receptor is coupled to the translocon, where the ribosome binds.
• Proteins are released inside the lumen for maturation or retained in the lipid bilayer as integral proteins if they have hydrophobic helices.
• Disulfide isomerase catalyzes disulfide bridges in the polypeptide chain.

Glycosylation of Proteins and Maturation

• Glycosylation is the addition of sugar motifs to eukaryotic proteins, serving as molecular flags or recognition signals.
• Specific amino acids are branching points for oligosaccharides.
• N-glycosylation occurs on asparagine in the ER.
• O-glycosylation occurs on serine in the Golgi apparatus.
• Monosaccharides are joined to dolichol in the RER by glycosyl transferase, then transferred to a protein by oligosaccharyl transferase.

Biosynthesis of Lipids and Proliferation of Membranes

• This function is common to both RER and SER.
• Most membrane lipids are synthesized by integral proteins in the ER.

Export of Vesicles to Golgi Apparatus

• RER lumen and membrane components can move between cisternae.
• Maturing products move toward the cisterna near the cis Golgi network.
• Vesicles bud from the ribosome-depleted RER in this region and are delivered to the Golgi in anterograde movement.
• The RER also receives vesicles from the Golgi in retrograde movement to compensate for membrane loss.

Explore the endoplasmic reticulum (ER) as part of the eukaryotic endomembrane system, including the Golgi apparatus, endosomes, and lysosomes. Learn about the roles of RER and SER in protein synthesis, lipid metabolism, and transport. Understand the function of the endomembrane system.