Some receptors are recycled during receptor mediated endocytosis o Others can be targeted for degradation Receptor downregulation can modulate signal transduction pathways LDL processing by cells Receptor Mediated Endocytosis o Low Density Lipoproteins LDL move cholesterol from liver to other body cells Large protein plus micelle of lipid cholesterol o LDL Receptor in coated pits binds LDL o Internalized by receptor mediated endocytosis o Early Endosome is a sorting compartment The receptor is sorted and sent back to the surface The LDL is sent on the lysosomes for processing o Late endosomes become multi vesicular to degrade targeted proteins while protecting others What s inside the vesicular bodies in the endosomes are degraded Mono ubiquitination tag proteins and target them for destruction in the cytoplasm ESCRT complex forms backwards buds in endosome membrane Subverted for HIV budding o Ubiquitinated viral Gag protein mimics Hrs protein triggers formation of ESCRT complex OUTWARD budding of Gag polymer shell and thus viral budding o Individuals with genetic disorders of cholesterol metabolism have defects in the delivery machinery If you lack receptor or have defective receptor you don t take up cholesterol efficiently leading to a high blood and low cellular concentration hypercholesterolemia Autophagy self eating o Delivers cytosolic proteins or entire organelles to lysosomes Exocytosis and Secretion o Vesicles bud from the TGN and move to the plasma membrane o Constitutive secretion secretory vesicles move to the plasma membrane and fuse dumping their contents outside the cell relatively constant rate o Regulated secretion In some cases the vesicles are held near the membrane until a stimulus is received and then they fuse The signals that sort these proteins are not well understoodcontents may aggregate in low pH environment of TGN The secretory vesicles accumulate in the cytoplasm When triggered by an external signal they fuse with the plasma membrane In some cases this is done to release a soluble protein in the vesicle into the outside environment Nerve impulse leads to secretion of neurotransmitter acetylcholine In some cases this is done in order to put a membrane protein onto the surface of the cell Insulin causes more glucose transporter to be put on the surface These are not actually causing secretion nothing is released from the cell but instead change the localization of membrane proteins o Some contents may be sorted to regulated secretory vesicles because they aggregate in the TGN Ex tightly packed histamine secretory vesicles released from mast cells when stimulated In polarized cells most cells in our bodies are polarized cells each end has a different compositions vesicles sort to different plasma membrane domains using a variety of mechanisms o Lipid Rans may help sort glycosphingolipids and GPI linked proteins to the apical end of cells o Some basal proteins have sorting signals in their tail o Transcytotic route through cells is yet another kind of sorting some cells send all proteins to basolateral membrane and then transcytosis moves a subset to the apical side o Distinct Rabs and SNARES are involved in sorting to domains Overview Signals in Membrane Trafficking o Proteins are made on cytoplasmic ribosomes except mitochondriaencoded proteins o If a hydrophobic start transfer sequence is made the protein enters the ER Golgi o Most things move to the Golgi o If a protein has an ER retention signal it recycles back to the ER o If it does not it goes on in the Golgi o Material moves through the golgi cisterna by cisternal maturation o Retention in the golgi is not well understood o If a protein has a lysosome signal patch it gets a Man 6 P and is sorted in the TGN to lysosomes o Otherwise it continues on to exocytic vesicles If it is a membrane protein it ends up in the plasma membrane LDL receptor If it is in vesicle lumen it is secreted Sorting signals for regulated secretion poorly understood Overview Membrane Sorting o Outward flow Membrane and membrane proteins move from ER to Golgi to secretory vesicles to plasma membrane Some material is diverted to lysosomes by Man 6 P signal Other material is delivered to secretory vesicles Some vesicles travel to plasma membrane and fuse constitutive Others move to plasma membrane but await a signal to fuse regulated Recycling of proteins and membrane occurs to return them to their correct location There is an inward flow of material through endocytosis and phagocytosis Some material fuses with lysosomes for degradation Some material is returned to the plasma membrane o Inward flowing material can also be diverted to other compartments transcytosis This is a very dynamic process The two systems must balance otherwise you will increase the amount of plasma membrane and lose internal membrane or vice versa
View Full Document
Unlocking...