o The endoplasmic reticulum (ER) by the nucleus has many ribosomes attached to it on the cytosolic side, giving its granular appearance, hence the name granular or rough ER.
o Translation on the rough ER propels proteins into the ER lumen as they are created.
o These proteins are tagged with a signal sequence of amino acids and sometimes glycosylated (carbohydrate chains are added – doesn’t occur in the cytosol).
o A 20 amino acid sequence called a signal peptide near the front of the peptide is recognized by protein-RNA signal-recognition particles (SRPs) that carries the entire ribosome complex to a receptor on the ER.
o The peptide is actually pulled through the membrane through an ATP driven process.
o The signal peptide is also usually removed by an enzyme.
o Some proteins have an ER retention signal which tells the ER that it is destined to function there, so if that protein escapes to the Golgi it will be returned to the ER.
o Rough ER has ribosomes attached to its cytosol side, and it synthesizes virtually all proteins not used in the cytosol.
o Proteins synthesized on the rough ER are pushed into the ER lumen and sent to the Golgi.
o The ER lumen is contiguous in places with the space between the double bilayer of the nuclear envelope.
Endoplasmic Reticulum Structure
Features of Endoplasmic Reticulum
o The newly synthesized proteins are moved through the lumen toward the Golgi apparatus or Golgi complex.
o The Golgi apparatus is a series of flattened, membrane bound sacs (cisterna) which are piled like stacks of plates.
o The Golgi apparatus is usually located close to the nucleus, and in animal cell is often close to the centrosome.
o Each Golgi stack has two distinct faces: an entry, or cis, face and an exit, or trans, face.
o The cis face is adjacent to the ER and the trans face is facing the cytosol.
o Small transport vesicles bud off from the ER and carry the proteins across the cytosol to the Golgi.
o Proteins are distinguished based upon their signal sequence and carbohydrate chains.
o Those proteins not possessing a signal sequence are packaged into secretory vesicles and expelled from the cell in a process known as bulk flow.
o The Golgi may change proteins chemically by glycosylation or by removing amino acids.
o The end product of the Golgi is a vesicle full of proteins.
o These protein filled vesicles may either be expelled from the cell as secretory vesicles, released from the Golgi to mature into lysosomes, or transported to other parts of the cell.
o The Golgi is like the post office it sorts and packages proteins.
o It can also alter proteins.
o Usually where proteins are modified and these modifications of the proteins determine where they will go.
o Secretory vesicles (sometimes called zymogen granules) may contain enzymes, growth factors, or extracellular matrix components.
o Secretory vesicles release their contents through exocytosis.
o Since exocytosis incorporates vesicle membranes into the cell membrane, secretory vesicles also act as the vehicle with which to supply the cell membrane with its integral proteins and lipids, and as the mechanism for membrane expansion.
o Secretory vesicles are continuously released by most cells in a process called constitutive secretion.
o Some specialized cells (ex. neuronal cells) can release secretory vesicles in response to a certain chemical (ex. Ca+2) or electrical stimulus in a process called regulated secretion.
o Ex. Neural synapses
o Some proteins are activated within secretory vesicles.
o (Ex. Proinsulin ⇒ insulin).
o Lysosomes contain acid hydrolases (hydrolytic enzymes) such as proteases, lipases, nucleases, and glycosidases.
o Together, these enzymes are capable of breaking down EVERY major type of macromolecule within the cell, including old organelles.
o Lysosomes generally have a pH of 5.
o They fuse with endocytotic vesicles and digest their contents.
o Any material not degraded by the lysosome is ejected from the cell through exocytosis.
o Under certain conditions lysosomes will rupture and release their contents into the cytosol killing the cell in a process called autolysis.
o This is useful in the formation of certain organs and tissues, like the destruction of the tissue between the digits of a human fetus in order to form fingers.
o Contain hydrolytic enzymes that digest substances taken in by endocytosis.
Smooth Endoplasmic Reticulum
o Smooth ER lacks ribosomes and contains an enzyme which is used in the liver, intestinal epithelial cells, and renal tubule epithelial cells, to make glucose from glycogen.
o Rough ER tends to resemble flattened sacs, whereas smooth ER tends to be tubular.
o Glucose ⇒ Glycogen = glycogenesis
o Glycogen ⇒ Glucose = glycogenolysis
o Triglycerides are produced in the smooth ER and stored as fat droplets.
o Adipocytes are cells containing predominately fat droplets.
o Such cells are important in energy storage and body temperature regulation.
o Adipocytes, also called fat cells, are specialized cells whose cytoplasm contains almost nothing but triglycerides.
o The Smooth ER and the cytosol share in the role of cholesterol formation and its conversion to various steroids.
o Most of the phospholipids in a cell membrane are originally synthesized in the smooth ER.
o The phospholipids are all synthesized on the cytosol side of the membrane and then some are flipped to the other side by proteins called phospholipid translocators located EXCLUSIVELY in the smooth ER.
o Smooth ER oxidizes foreign substances, detoxifying drugs, pesticides, toxins, and pollutants.
o The Smooth ER is the site of lipid synthesis, including steroids, detoxifying drugs, and useful for converting glycogen to glucose.
o Peroxisomes are vesicles in the cytosol that grow by incorporating lipids and proteins from the cytosol.
o Rather than budding off membranes like lysosomes from the Golgi, peroxisomes are self-replicating.
o They are involved in the production and breakdown of hydrogen peroxide.
o Peroxisomes inactivate toxic substances such as alcohol, regulate oxygen concentration, play a role in the synthesis and break of lipids, and in the metabolism of nitrogenous bases and carbohydrates.
Endoplasmic Reticulum Citations
- Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications. FEBS J . 2019 Jan;286(2):241-278.
- The endoplasmic reticulum: structure, function and response to cellular signaling. Cell Mol Life Sci . 2016 Jan;73(1):79-94.
- The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol . 2015;10:173-94.
- Endoplasmic Reticulum redox pathways: in sickness and in health. FEBS J . 2019 Jan;286(2):311-321.
- Endoplasmic reticulum stress: a key player in human disease. FEBS J . 2019 Jan;286(2):228-231.
- Endoplasmic reticulum quality control by garbage disposal. FEBS J . 2019 Jan;286(2):232-240.
- Form follows function: the importance of endoplasmic reticulum shape. Annu Rev Biochem . 2015;84:791-811.
- Endoplasmic Reticulum: Target for Next-Generation Cancer Therapy. Chembiochem . 2018 Nov 16;19(22):2341-2343.
- Endoplasmic reticulum in viral infection. Int Rev Cell Mol Biol . 2020;350:265-284.
- Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol . 2007 Jul;8(7):519-29.