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Lecture 4

LECTURE 4.docx

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Steve Joordens

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LECTURE 4SLIDE 6In the cis Golgi lysosomal proteins have mannose on them and they get phosphorylated via kinase enzymeThis is the signal that tells the cell to direct it to the lysosomeMannose6Phosphate binds to M6P receptor located on trans GolgiClathrin is like the COP proteins that helps make vesicles bud Clathrin binds to M6P receptor on the cytosolic faceThe vesicle then pinches off and fuses to late endosomes which mature into lysosomesThe receptors then go back into the trans Golgi recycledSLIDE 7Lysosomal enzyme is made in the ER once it enters the Golgi the sugar is phosphorylated Then it goes to trans Golgi and associates with receptors On the cytosol side Clathrin helps form vesicles and then it fuses with late endosomesSLIDE 8There were people who had lysosomes filled with undigested material The problem was that enzymes werent getting directed properly and getting secretedThis is called icell disease They purified secreted lysosome enzymes and compared it with normal patients They discovered was that they were missing the enzymes that phosphorylate mannoseAs a result the lysosome enzymes are secreted which is the default functionSo if your protein doesnt have KDEL that keeps it in ER doesnt have Golgi signature doesnt have mannose6phosphate the default is secretionSLIDE 9Enzymes hydrolyze macromolecules if its not acidic enough they wont workAll cells have them but immune cells have a lot moreSLIDE 10Lysosomes have many proton pumps that drive hydrogen into the lumen of the lysosome
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