Organelles 3 Flashcards
Functions of the Golgi
- Sorting and dispatching station for proteins and lipids made in ER
- Modification of N-linked oligosaccharide chains on glycoproteins made in ER
- Synthesis of O-linked oligosaccharides on proteins and lipids made in ER
- Sythesis of glycosaminoglycan chains on core proteins of proteoglycans
Structure of Golgi
- Flattened membrane-bounded cisternae stacked together (3-20 per golgi) stack
- Cis face (entry face) is adjacent to the ER
- Trans face (exit face) points toward the plasma membrane
- Network of interconnected tubular and cisternal structures from the cis and trans golgi networks at either end of the stack
- Typically located near the cell nucleus
- Number of golgi stacks per cell depends on the cell type
Cis Golgi network
Sorts proteins that need to be returned to the ER (have an ER retention signal)
Signal binds a specific receptor in Cis golgi network transport vesicles that return to the ER
Trans Golgi network
Sorts proteins destined for lysosomes or regulated secretion from those that will continue to the plasma membrane via the default pathway
Modification of N-linked Oligosaccharides in the Golgi
- Glycosidases can remove sugars
- Glycosyl transferases can add sugars
- Degree of modification can vary (3 classes: High mannose, complex, hybrid)
O-linked glycosylation in the Golgi
- Covalent attachement of oligosaccharides to the OH groups of serine or threonine residues in proteins.
- Sugars are added to proteins one at a time
- Sugars are added post-translationally with the use of specific glycosyltransferases
Proteoglycans
- Typically contain more than 95% carbohydrate by mass and a small core protein.
- Carbohydrate portion always consists of glycosaminoglycan chains which are linear polymers of a repeating disaccharide unit that are hundreds of sugars long
- High density of negative charges due to carboxyl and sulfate groups
- Attract water well (form gels and lubricants)
- Come in a variety of sizes with varying numbers and types of glycosaminoglycans attached (most link to a serine residue)
6 classes of glycosaminoglycans
Chondrotin sulfate Dermatan sulfate Keratan sulfate Heparin Heparin sulfate Hyaluronate
Synthesis of proteoglycans
- Occurs in the golgi
- Core protein is synthesized in the ER and then transported to the golgi
- In the golgi a series of different glycosyltransferases act sequentially to build the 4 sugar linker region on the serine of the core protein
- Repeated action of two specific glycosyltransferases adds the sugars of the repeating disaccharide unit one at a time to build the glycosaminoglycan
- Additional enzymes modify the sugars as the chain is elongating
Lysosomal hydrolases
Proteases and glycosidases
Degrade glycoproteins and proteoglycans in the lysosomes
Endoglycosidases
Remove carbohydrates from the protein in glycoproteins and proteoglycans
Proteases
Cleave the protein component of glycoproteins and proteoglycans into amino acids that can be reused by the cell.
Glycosidases
Specific glycosidases act on each glycosidic bond in serial fashion in reverse order to that in which they were added
Glycoprotein
Any protein with one or more covalently bound carbohydrate units that do not contain a serial repeat unit; typically, but not always, they are mostly protein with a little carbohydrate attached.
Proteoglycan
Any protein with one or more covalently bound glycosaminoglycan chains; typically, but not always, they are mostly carbohydrate with a very small core protein.
Biological functions of glycoproteins
- Extracellular matrix (structure/support)-collagen, fibrin
- Hormones- FSH, CG
- Lubrication and protection- mucins, mucus secretions of GI
- Enzymes- proteases, glycosidases, hydrolases
- Immunologic molecules- immunoglobulins, complement, interferon
- Cell surface antigens- ABO blood group antigens
- Plasma proteins- blood clotting factors
-Glycocalyx- thick layer of carbohydrate on cell surface
Mucins
- Viscous glycoproteins composed of 80% carb by mass
- Mostly O-linked
- Rod shaped with central region of Ser and Thr (for O-linking)
- Important for mucus in epithelial surfaces
- Polymerization and high density of carbs allows the glycoproteins to generate a hydrated gel
A blood allele
Encodes a transferase that transfers an N-acetyl galactosamine
-Codominant with B allele
B blood allele
Encodes a transferase that transfers a galactose
Differs from A allele by only 4 aa
Codominant with A
O allele
Encodes a nonfunctional protein due to a single nucleotide deletion that causes a frameshift
Recessive
Two exocytosis pathways
Constitutive exocytosis pathway
-default pathway–go to the plasma membrane
Regulated exocytosis pathway (clathrin-coated vesicles)
- found in specialized secretory cells such as those that secrete large quantities or hormones or digestive enzymes
- Proteins diverted into secretory vesicles
- Vesicles will only fuse in response to an extracellular signal
- Aggregate into the trans golgi network
Two types of endocytosis
Pinocytosis
- via small vesicles, classical endocytosis
- take up fluid and macromolecules
- clathrin coated pits
- can be receptor mediated
Phagocytosis
- Large particles ingested via phagosomes, requires receptor activation at cell surface
- Macrophages and neutrophils
Uptake of cholesterol
- Receptor mediated endocytosis
- Most blood cholesterol transported as low density lipoprotein (LDL)
- When cholesterol needed for membrane synthesis cells make LDL receptors and insert them into plasma membrane
- LDL receptors associate with newly forming clathrin-coated pits and are internalized along with any bound LDL particles in clathrin coated vesicles
- Vesicles shred clathrin coats and fuse with early endosomes, LDL dissociates from receptor
- LDL transported to lysosomes and hydrolyzed to free cholesterol which is then released into the cytosol for membrane synthesis
- LDL receptor us recycled back to plasma membrane from the early endosome
Familiar hypercholesterolemia
LDL receptors are defective, cholesterol accumulates in the blood and forms plaques
