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Lecture 19

BIOL 201 - Lecture 19

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Biology (Sci)
BIOL 201
Greg Brown

Lecture 19 The lysosome is the organelle for degradation of different components, especially proteins and lipids which enter the cell and can be broken down into their constituents. Helps recycle non- functional proteins, for example. Proteins destined for lysosome have internal signals that are recognised by an enzyme in the cis-Golgi which attaches to a phosphate group on the manos sugar. This serves as a signal to target the proteinto the lysosome. Targeting occurs through a membrane protein located in the trans-golgi-network, Manos- 6-Phosphate receptor (M6P) • In TGN, lysosomal proteins with M6P modification bind to M6P receptor. AP1- clathrin complex assembles at M6P receptor – mediated by ARF • Clathrin coated vesicle buds from trans- Golgi, coat dissociates • Vesicle fuses with late endosome, low pH leads to protein dissociation from receptor. • Receptor vesicle re-fuses with trans-Golgi, transport vesicle fuses with lysosome • Many secreted proteins (such as insulin) are synthesized as large “proproteins”. • Insulin is synthesized as pre-pro-insulin, which isconverted to proinsulin in the ER. It moves into secretory vesicles in this form. • Proinsulin → insulin • The pancreas receives a signal to secrete insulin after blood glucose rises. • Proinsulin antibodies stain particles pinching off from trans-golgi. Insulin antibody stains mature secretory vesicles. (Incredibly high insulin concentrations) • Conversion of proinsulin to insulin involves multiple cleavage events and three different proteases • Proteolytic processing of proproteins occurs aftervesicle pinches off from TGN Receptor mediated endocytosis • Endocytosis: formation of vesicles at plasma membrane for internalization of extracellular material • Receptor mediated endocytosis: receptor on plasma membrane binds extracellular macromolecule, formation of endocytic transport vesicle for delivery to late endosome • Mediated by clathrin/AP2 vesicles • Site of vesicle formation on plasma membrane is called a clathrin coated pit • Mechanism for internalization of many proteins e.g. insulin, transferrin Low density lipoprotein (LDL) particles • Helped study transport vesivles
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