Neurotransmitter Storage and Release 8/24/2018 Neurotransmitter Storage and Release Ca2+ VGCC +ATP P CaM Ca2+-CaM Ca2+-CaMK K -P -P P VGCC: voltage-gated calcium channel CaM: calmodulin K: kinase (I or II) ATP: adenosine triphosphate P: phosphate ……….. Eric Niederhoffer SIU-SOM

Vesicle Fusion ……….. NT VT Ac Botulinum and Tetanus toxin 8/24/2018 Vesicle Fusion ……….. NT VT Ac Botulinum and Tetanus toxin Storage and release complex Syn Docking and fusion complex VT: vesicle transporter Ac: actin Syn: synapsin NT: neurotransmitter CaMK: calmodulin kinase Synp: synaptophysin Synb: synaptobrevin (R motif) = VAMP VAMP: vesicle-associate membrane protein (recycled with vesicles) Synx: syntaxin (Qa motif) Synt: synaptotagmin, Ca2+ sensing, interacts with syntaxin Nr: neurexin (alignment of vesicles) Rab3: GTP-binding protein, recruitment of vesicle docking proteins SNAP: soluble NSF attachment proteins, NSF - N-ethylmaleimide-sensitive fusion protein, SNAP25 (Qb, Qc motifs) SNARE: synaptosome-associated receptor, SNARE motifs (R, Qa, Qb, Qc) v-SNARE: vesicle SNAP receptor (synaptobrevin) t-SNARE: target SNAP receptor (syntaxin, SNAP23, SNAP25), most remain associated with plasma membrane Complexin arrests hemifusion complex (VAMP, SNAP25, syntaxin-1A), synaptotagmin relieves complexin arrest CaMK Synp SNAP 23 25 v-SNARE Synb VAMP Synx Nr Synt Rab3 Ca2+ t-SNARE

8/24/2018 Review Questions How are neurotransmitters packaged and released (signal transduction pathway, second messenger, transporters, receptors)?