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Cells internalize macromolecules, particulate matter receptor- |
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- actually have cells engulfing large particles or other cells |
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Specialized cases are phagocytosis |
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- taking in extracellular fluid called pinocytosis |
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Membrane-bound compartments'
Composition of each is different - enzymes and pH Early endosomes, Late endosomes and Lysosomes |
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Why are there different compartments for endocytosis? |
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Early endosomes - recycling and sorting pH differences are important for conformation changes in proteins…function Acid hydrolases (enzymes) |
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Receptors often release ligands |
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At low pH, conformational change to amino acids of receptor |
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occurs allowing release of ligand |
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Intracellular digestion of macromolecules Production of nutrients for the cell |
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- meaning, they only work at low pH |
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low pH in lysosomes (Vacuolar H+ATPase) |
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Late Endosomes/Multivesicular Bodies (MVB) |
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Receptor mediated endocytosis Transport of cholesterol |
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Familial hypercholesterolemia |
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Receptor mediated endocytosis Transport of iron |
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Transferrin release or iron and receptor recycling |
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Transport of growth factors |
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Internalization via clathrin-coated pits Binding of ligand to a receptor |
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- LDL (low density lipoprotein) is a lipid-protein particle that binds and transports cholesterol to cells Atherosclerosis |
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- too much in blood can lead to plaques |
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- carries cholesterol back to liver where it is passed from body |
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- fat made in body (high levels signal problems) |
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Signal peptide for clathrin-coated pits: |
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- hydrophobic aa LDL receptor uses NPVY Binding of signal peptide to adaptin signals internalization |
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Receptor recycles for additional rounds of endocytosis (lifespan approximately 20 hours and in that time, it is estimated it can make the trip 700 times) |
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is a soluble protein that transports iron in the blood to cells low pH releases iron, not transferrin from receptor |
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stores iron and releases it at appropriate times |
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Myoglobin, Cytochromes, and proteins required for DNA synthesis also need iron |
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Iron binds to apotransferrin in blood Transferrin (now bound to iron) binds to cell surface receptor (transferrin receptor) |
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Receptor internalized via clathrin- |
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mediated endocytosis At pH of early endosome, Fe is released from Transferrin Transferrin, still bound to receptor, is transorted back to plasma membrane via fast recycling pathway (regulated by Rab4) |
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(neutral pH), the apotransferrin is released from the receptor to go collect more Fe from the system |
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Epidermal growth factor receptors (Erbs) ErbB2 associated with breast and ovarian cancer |
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Activated receptors (ligand-bound, dimers) signal via |
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Only when internalized into the MVB is the cytosolic domain |
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no longer able to signal in the cytosol |
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Multivesticular bodies receptor down |
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-regulation signal transport to lysosomes |
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- serves as a sorting signal for internalization into internal vesicles within MVB |
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Not everything is take into cells by |
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Beyond clatherin, things taken into cell |
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Specialized lipid-raft structure called calveolae protein found here called caveolin flask-like structures Important for some viruses |
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cell drinking Small vesicles occurring constantly and at a fixed amount |
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ingest 100% of their membrane every 1/2 hour Why don’t cells shrink away to nothing? |
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Large particle - even other cells
Endosomes called Phagosomes Immune system - macrophage, neutrophils and dendritic cells - professional phagocytes |
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Polorized cells, Transcytosis - |
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transport from one side to the other - apical to basolateral or vice versa |
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Notice - two sets of early endosomes |
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One specific case - transfer of maternal IgG to the fetus |
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Different Means for Internalization |
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Receptor-mediated endocytosis Clathrin-mediated Non-clathrin-mediated Caveoli-mediated internalization Phagocytosis Pinocytosis Other |
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