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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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Definition
| Transferrin release or iron and receptor recycling |
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| Transport of growth factors |
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Definition
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| Internalization via clathrin-coated pits Binding of ligand to a receptor |
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Definition
- 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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Definition
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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Definition
| no longer able to signal in the cytosol |
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| Multivesticular bodies receptor down |
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Definition
-regulation signal transport to lysosomes |
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Definition
| - 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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Definition
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| Beyond clatherin, things taken into cell |
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Definition
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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Definition
| 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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Definition
| One specific case - transfer of maternal IgG to the fetus |
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| Different Means for Internalization |
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Definition
Receptor-mediated endocytosis Clathrin-mediated Non-clathrin-mediated Caveoli-mediated internalization Phagocytosis Pinocytosis Other |
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