Endoplasmic reticulum (ER) is a membrane-like organelle in cytoplasm of eukaryotic cells. It constitutes half of the endomembrane system. The contact area is increased by ER and numerous enzymes are host on its surface. This structure not only accelerates biochemical reactions but also partitions cytoplasm into several distinct regions to prevent interference between life activities. Besides nucleic acids, it is base for the synthesis of biological macromolecules such as protein, lipid, and carbohydrate.
To better understand these benefits, we need to look at how prokaryotes work. Although they lack an ER and other organelles, their very small size results in a high surface area-to-volume ratio. Plasma membrane and its invaginations are sufficient to sustain life activities. However, eukaryotes are over ten times larger in diameter; the volume is 1000-10000 times larger, as it is proportional to cube of diameter; the volume-to-area ratio is around 0.1, as it is proportional to diameter inversely. Therefore, were an endomembrane system absent, it would prevent eukaryotic cells from normal metabolism, and they wouldn't grow so large.
ER originates from nuclear envelope, and extends to plasma membrane along microtubules under the guidance of motor proteins. Its lumen is continuous with perinuclear space. As it’s closely related with nucleus, some believe both ER and nuclear envelope evolved from the invaginated cell membrane in prokaryotes. It is a dynamic organelle. The quantity, distribution, and ratio of two forms are dependent to cell type, growth stage, and metabolic demand.
Rough ER: Protein Modification
Typically, proteins in cytoplasm are synthesized on free ribosomes. Others are manufactured on the RER: proteins secreted outside, such as collagen in the extracellular matrix, antibodies, and digestive enzymes; transmembrane proteins; and some water-soluble proteins in organelles like hydrolases.
Free ribosomes synthesize polypeptide based on templates provided by mRNA. They are captured by receptors on Rough ER because of the special amino acid sequences. Sometimes, synthesis continues on ribosome attached here, and mitochondria cluster nearby to supply with energy. Thus, rough ER is always studded with ribosomes in its outer surface, and it seems a little "rough" under an electron microscope. Polypeptides enter ER cavity to fold into more complex structures. One of the most common modifications is N-glycosylation whose oligosaccharide is linked to Asp. After leaving here, they undergo further chemical modifications in Golgi apparatus. The introduction of fatty acids through acylation is another modification. Common examples include myristic acid covalently linked to N-terminus and palmitic acid forming a thioester bond with Cys.
The ER is not only a processing factory but also a quality control monitor in protein secretion pathway. Some simple polypeptides spontaneously fold into bio active conformations invitro. However, in the ER, they are interfered by surrounding molecules and need chaperones. Some chaperones adhere to hydrophobic regions to prevent aggregation. Others encase polypeptides like a cage to promote their complete proper folding. The assembly of multi-subunit proteins also occurs here. Misfolded ones are recaptured for repairing until they achieve the correct shape. If repeated attempts fail, they are transported back to cytoplasm for degradation via ubiquitin-dependent pathway. Proteins remain here for several minutes to acquire correct conformation. Additionally, disulfide bond and collagen hydroxylation also occur here.
Rough ER is highly developed in cells with secretion tasks, such as digestive gland cells, nerve cells, and plasma cells. Guess what substances they are producing.
Smooth ER: Lipid Systhesis, Detoxification
It has a tubular structure whose surface is lack of ribosomes, so it has a smooth appearance under an electron microscope. Phospholipid synthesis is conducted on its outer surface. Then they are transferred to inner surface to ensure symmetrical growth of bilayer membrane. Phospholipids are released from here via three pathways. Vesicles budding from the smooth ER transport them to other organelles or plasma membrane. They form water-soluble complexes with phospholipid exchange proteins and enter the cytoplasm. When encountered, they insert into the target membrane. Direct contact between ER and other parts of endomembrane system is another method. Smooth ER is also responsible for fat and steroid production, which are transferred out similarly.
Smooth ER in liver cell has detoxifying enzyme systems. Their strategy is to introduce hydrophilic groups into toxins to make them more soluble. The most abundant and familiar one is cytochrome P450. Toxic compounds are hydroxylated to facilitate their combination with glucuronic acid, acetate, amino acids, sulfate, or glutathione in subsequent biochemical reactions. Modified toxins are weakened and transported to Golgi apparatus. Then, they are either excreted into the intestine via bile or enter the bloodstream via extracellular fluid, from which they are excreted into kidneys. Therefore, when organisms face toxin attacks, P450 is synthesized in large amounts. The smooth ER area increases several times within days, and they perish through lysosomal autophagy once the crisis is over.
Calcium ions act as second messengers in intracellular signal transmission. Calcium ions are pumped into smooth ER lumen for storage. When cells receive extracellular signals, calcium ions release into the cytoplasm to activate calcium-dependent metabolism, such as muscle contraction and neurotransmitter release.
If a cell's important tasks are lipid synthesis and detoxification, they have a well-developed smooth ER, such as cells in liver cells and gonadal.