MED1003 Week 4 Seminar: The Endomembrane System and Peroxisomes PDF

The endomembrane system and peroxisomes I by Siu Wai (Phyllis) TSANG, PhD TUNG WAH COLLEGE email: [email protected] Office#: 3190-6713 Prepared by SWT 2024 email: [email protected] 1  The endomembrane system...

The endomembrane system and peroxisomes I by Siu Wai (Phyllis) TSANG, PhD TUNG WAH COLLEGE email: [email protected] Office#: 3190-6713 Prepared by SWT 2024 email: [email protected] 1  The endomembrane system Textbook Ch.12 p.339 The endomembrane system of eukaryotic cell consists of the 1. endoplasmic reticulum (ER), the 2. Golgi apparatus, 3. endosomes, & 4. lysosomes It is associated with both the nuclear envelope and the plasma membrane The movement of proteins and lipids between organelles, known as trafficking, must be tightly regulated 2 Prepared by SWT 2024 email: [email protected]  The endomembrane system (cont’d) Textbook Ch.12 p.339 Material flows from the ER to and from the Golgi apparatus, endosomes and lysosomes by means of transport vesicles that shuttle between the various organelles These transport vesicles carry membrane lipids and membrane-bound proteins to their proper destinations in the cell or destined for secretion 3 Prepared by SWT 2024 email: [email protected] The endomembrane system – Endoplasmic reticulum (ER) Prepared by SWT 2024 email: [email protected] 4 Endoplasmic reticulum (ER) The endoplasmic reticulum (ER) is a continuous network of flattened sacs, tubules, and associated vesicles that stretches throughout the cytoplasm of the eukaryotic cell Endoplasmic means “within the (cyto)plasm” Reticulum means “network” The membrane-bounded sacs (flattened sacs) are called ER cisternae https://cdn.britannica.com/79/117279-050-3AE0F00F/membrane- The space enclosed by them is called the ER lumen system-Endoplasmic-reticulum-cells-biosynthesis-transport.jpg ER is not visible by light microscopy unless stained Prepared by SWT 2024 email: [email protected] 5 The two basic kinds of ER Textbook Ch.12 p.340 Prepared by SWT 2024 email: [email protected] 6 Rough endoplasmic reticulum (rough ER) With ribosomes attached to the cytosolic side Membranes form large flattened sheets A portion of the rough ER forms transition vesicles that shuttle lipids and proteins from the ER to the Golgi apparatus The ribosomes attached to the cytosolic side of rough ER are responsible for synthesizing both membrane-bound and soluble proteins Prepared by SWT 2024 email: [email protected] 7 Rough ER (cont’d) In rough ER, a host of enzymes catalyze co-translational and posttranslational modifications Glycosylation (carbohydrate addition) Folding of proteins Assembly of multimeric proteins A site for “Quality control”: In ERAD (ER-associated degradation, the improperly folded / assembled / modified proteins are degraded by cytosolic proteasomes instead of moving on to the Golgi apparatus Several human diseases, including familial hypercholesterolemia 高膽固醇血症, are associated with defects in these processes Prepared by SWT 2024 email: [email protected] 8 ER-associated degradation Misfolded proteins are recognized by various ER factors, such as chaperones To maintain ER homeostasis, proteins that fail to obtain their proper native structure must be eliminated from the ER via the ER-associated degradation (ERAD) https://ars.els-cdn.com/content/image/1-s2.0-S1876162319300641-gr2.jpg Prepared by SWT 2024 email: [email protected] 9 Smooth endoplasmic reticulum (smooth ER) Textbook Ch.12 p.342 Without ribosomes attached to the membrane Membranes form tubular structure Involved in carbohydrate metabolism Smooth ER assists in the enzymatic breakdown of stored glycogen Membranes of the smooth ER in liver cells contain glucose-6-phosphatase An enzyme that breaks down glucose-6-phosphate into free glucose and inorganic phosphate (Pi) Free glucose is then transported out of the liver cell by a glucose transporter in the plasma membrane Prepared by SWT 2024 email: [email protected] 10 Detoxification in smooth ER Drug detoxification often involves enzyme-catalyzed hydroxylation the addition of hydroxyl groups to hydrophobic drugs makes them more soluble and easier to excrete from the body catalyzed by cytochrome P-450 enzymes (monooxygenases) with e- transfer from NAD(P)H RH + NAD(P)H + H++ O2  ROH + NAD(P)+ + H2O Prepared by SWT 2024 email: [email protected] 11 Calcium storage in smooth ER In muscle cells, the smooth ER lumen contains high concentrations of calcium-binding proteins Calcium ions are pumped into the ER by ATP- dependent calcium ATPases and are released in response to extracellular signals to aid in muscle contraction Prepared by SWT 2024 email: [email protected] 12 Steroid biosynthesis in smooth ER The smooth ER in certain cells is the site of biosynthesis of cholesterol and steroid hormones (e.g., cortisol, testosterone and estrogen) Hydroxymethylglutaryl-CoA reductase (HMG-CoA +space+filling+model+of+the+steroid+hormone+cortisol..jpg https://slideplayer.com/slide/14092860/86/images/32/A+3D reductase) is present in smooth ER which is important in cholesterol biosynthesis The ER is the primary source of membrane lipids, including phospholipids and cholesterol Prepared by SWT 2024 email: [email protected] 13 The ER membrane Although the ER is the source of most membrane lipids, the compositions of other cellular membranes vary significantly from the composition of the ER membrane ER membranes are about 5 nm thick, whereas cell membranes are about 8 nm thick Textbook Ch.12 p.343 Prepared by SWT 2024 email: [email protected] 14 The endomembrane system – The Golgi Apparatus Prepared by SWT 2024 email: [email protected] 15 Golgi apparatus The Golgi apparatus is a series of flattened membrane- bound cisternae, disk-shaped sacs that are stacked together (Golgi complex) Usually, there are 3−8 cisternae per stack Medial Golgi network: located in the middle Cis-Golgi network (CGN): closest to ER Trans-Golgi network (TGN): farthest from ER, closest to Textbook Ch.12 p.344 cell surface At the trans face, transport vesicles bud from the TGN and carry lipids and proteins to other components of the endomembrane system Prepared by SWT 2024 email: [email protected] 16 The flow of lipids and proteins TWO models proposed for the movement of lipids and proteins from the CGN to the TGN via the medial cisternae of the Golgi apparatus The stationary cisternae model Shuttle vesicles carry material forward from the ER to successive Golgi compartments, which remain in place The cisternal maturation model (membrane flow) The cisternae gradually change in composition as they themselves move forward In both models, enzymes and lipids needed in earlier compartments move backward in retrograde fashion Textbook Ch.12 p.345 Prepared by SWT 2024 email: [email protected] 17 Two models for movement through the Golgi The two models are not necessarily mutually exclusive Both may apply to some degree, depending on the organism and the role of the cell The movement from ER through the Golgi apparatus toward the plasma membrane is called anterograde transport The flow of vesicles from Golgi cisternae back toward the ER is called retrograde transport Every time a secretory granule fuses with the plasma membrane and discharges its contents by exocytosis, a bit of membrane that originated in the ER becomes a part of the plasma membrane The cell recycles lipids and proteins no longer needed during the late stages Prepared by SWT 2024 email: [email protected] 18 Trafficking through the endomembrane system Textbook Ch.12 p.348 Prepared by SWT 2024 email: [email protected] 19 Glycosylation The addition of carbohydrate side chains (glycan) to specific amino acid residues of proteins, forming glycoproteins Much of the protein processing carried out Textbook Ch.12 p.346 within the ER and Golgi apparatus involves glycosylation Two general kinds of glycosylation: N-linked glycosylation (or N-glycosylation) The glycan is added to a nitrogen atom O-linked glycosylation The glycan is added to an oxygen atom Prepared by SWT 2024 email: [email protected] 20 Transporting materials across membrane Two methods of transporting materials across the plasma membrane Exocytosis The process by which secretory granules release their contents to the exterior of the cell Secretory pathways by which proteins move from the ER through the Golgi apparatus to secretory vesicles and secretory granules Endocytosis The process by which cells internalize external materials A small segment of the plasma membrane progressively folds inward and then pinches off to form an endocytic vesicle containing ingested substances or particles Both processes are unique to eukaryotic cells and are also involved in the delivery, recycling, and turnover of membrane proteins Prepared by SWT 2024 email: [email protected] 21 Transporting materials across membrane Textbook Ch.12 p.353-5 Prepared by SWT 2024 email: [email protected] 22  https://open.oregonstate.education/app/uploads/sites/178/2023/11/FIgure-04-01.png Prepared by SWT 2024 email: [email protected] 23 ~ The end ~ Prepared by SWT 2024 email: [email protected] 24