lect21-08 - Zoo 523 Lecture 21 2008 Reading pp261-263 and...

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Zoo 523 Lecture 21 2008 Reading: pp261 -263 and 244 - 250 SECRETION: In the cytoplasm there is a whole pathway involved in generating synaptic vesicles. You start off in the cell body with the rough endoplasmic reticulum (RER) where the proteins get made. The proteins get inserted into the lumen of the RER, and then get processed by the Golgi apparatus, a stack of compartments like this [diagram] and then there are secretory vesicles, and then there is the process of secreting the contents of the secretory vesicles, and then there is the process of reuptake of membrane -- endocytosis. Proteins get shoved into the RER, and then they get processed through the Golgi, where they are e.g. glycosylated, and undergo other post-translational modifications. This happens in different compartments of the Golgi. There are different enzymes for doing different parts of the post-translational modification, in each of these different compartments. In order to get these proteins into these different spaces, you have a process of budding from the RER, formation of these vesicles, and fusion with the cis Golgi. In order to get transport of proteins between the different compartments of the Golgi, you have budding off of vesicles from one compartment, and fusion with the next compartment, and so on, and finally, budding off from the trans-Golgi to produce secretory vesicles. This process, in the cell body, involves the pinching off of these things by a protein called coatamer. In the nerve terminal, in the process of endocytosis, in the taking up of stuff into the nerve terminal, the protein forming the coat around the endocytic vesicles is called clathrin, as we already discussed. Clathrin is a protein with 3 spokes. Clathrin molecules like to associate with one another and form a hexagonal array [diagram], which leads to the formation of a basket-like network of clathrin molecules. As the array gets bigger, it tends to form a curved shape. So this is how the endocytic pit gets formed. The final act of creating the endocytic vesicle is to pinch off the membrane from the presynaptic membrane. This involves another protein called dynamin, which basically gets a stranglehold on the neck of the pit and squeezes until the membrane closes. Then you have a coated vesicle. There's no evidence that in neurons this endocytic process involves coatamers -- it involves clathrin. In the delivery of synaptic vesicles to the synaptic terminal, it turns out that they are transported down the axon by fast axoplasmic transport, in the form of larger vesicles, which fuse with the presynaptic membrane, and then this membrane is taken back up into the terminal by endocytosis, into the recycling mechanism that gives rise eventually to coated vesicles, and then to synaptic vesicles, which are smaller than the transport vesicles. It's not clear yet (in that mechanism I gave you for recycling last time) exactly what's going on. The experiment I mentioned last time,
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lect21-08 - Zoo 523 Lecture 21 2008 Reading pp261-263 and...

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