Lecture10v5 - Lecture 10 SV cycle continued . . . Lifecycle...

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Lecture 10 – SV cycle continued . . . Lifecycle of Neurotransmitters in the Brain http://www.about-dementia.com/articles/images/ParkinsonsDopamine.jpg The boxer Muhammad Ali and the actor Michael J. Fox suffer from Parkinson's disease. Both have supported efforts to find a cure. student.britannica.com
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Two Super Families of Neurotransmitter Receptors Iontropic receptors Metabotropic receptors
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Overview for lecture 9 1.Synaptic Vesicle cycle Steps in Exocytosis Molecules involved in Exocytosis Endocytosis 2. Life Cycle of a Neurotransmitter Synthesis Storage Release Termination (clearance) Uptake
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http://scienceblogs.com/purepedantry/2006/12/presynaptic_vesicles_are_hemif.php Molecular Steps in Synaptic Vesicle Cycle Immobilization in Reserve Pool 1. NT is taken up into SV 1. These vesicles “wait” until needed In what is referred to as the “reserve pool
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Immobilization in Reserve Pool Molecule #1, #2, #3 : Synapsin reversibly binds to SV and crosslinks vesicles to actin to tether the vesicles in the reserve pool. This reaction is reversible by the phophorylation of synapsin by CamKII. http://www.biochemj.org/bj/373/0641/bj3730641f04.gif
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Once the vesicle is released how does it target the active zone to be docked? Rab3 is a small GTPase Rab3 complexed to GTP binds to synaptic vesicles. During the targeting of the SV to the active zone Rab3 hydrolyzes its bound GTP to GDP.
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Molecular Steps in Synaptic Vesicle Cycle Docking Vesicles move from the reserve pool into the active zone where they “dock”. Blue vesicles are docked but not fused in the Active Zone http://scienceblogs.com/purepedantry/2006/12/presynaptic_vesicles_are_hemif.php
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Vesicle Cycle – Priming Pre- Fusion Vesicles Docked in Active Zone Red Vesicles “primed” in Active Zone http://scienceblogs.com/purepedantry/2006/12/presynaptic_vesicles_are_hemif.php Prefusion primes the vesicles for calcium-triggered exocytosis ** Contraversial as to whether this step involves a partial fusion reaction – known as Hemifusion.
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Vesicle Cycle – Calcium triggered exocytosis •Action Potential invades the nerve terminal opening voltage-gated calcium channels causing calcium to flow down it’s concentration gradient into the presynaptic terminal and bind to a calcium sensor located on the SV. •The SV completely fuses with the membrane releasing NT into the synaptic cleft where it can bind to postsynaptic receptors and depolarize the postsynaptic cell.
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A closer look at the molecules involved in Calcium triggered exocytosis SNARE Complex: VAMP (aka synaptobrevin), Syntaxin , SNAP25 , And the syntaxin binding Protein nsec1 (munc 18) Calcium sensor http://neuroscience.uth.tmc.edu/s1/i10-4.html
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proteins fuse upon the displacement of n- sec-1. A closer look at the molecules
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Lecture10v5 - Lecture 10 SV cycle continued . . . Lifecycle...

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