Development of Microfluidic Applications to Study the Role of Kainate Receptors in Synaptogenesis

................................................................................................................................ 1 1 Literature Review ............................................................................................................... 2 1.1 Kainate Receptors ........................................................................................................ 2 1.1.1 Subunit composition and structure of Kainate Receptors ................................... 3 1.1.2 RNA editing of the KAR subunits .......................................................................... 4 1.1.3 Post translational modifications ........................................................................... 6 1.2 Subcellular distribution of Kainate Receptors and Trafficking .................................... 6 1.2.1 Exocytosis from ER to the surface ........................................................................ 7 1.2.1.1 Synaptic targeting .............................................................................................. 9 1.2.2 Kainate Receptor endocytosis and degradation ................................................ 11 1.3 KAR Signaling Pathways ............................................................................................. 12 1.3.1 Ionotropic signaling ............................................................................................ 12 1.3.2 G protein-coupled signaling................................................................................ 13 1.4 Physiological Functions .............................................................................................. 14 1.4.1 Presynaptic KARs: Modulation of neurotransmitter release ............................. 15 1.4.2 Postsynaptic Kainate Receptors ......................................................................... 16 1.4.3 Role of KARs in synaptic plasticity ...................................................................... 17 1.5 Synaptogenesis .......................................................................................................... 18 1.5.1 Synapse progenesis ............................................................................................ 18 1.5.2 Pre and postsynaptic differentiation .................................................................. 19 1.5.2.1 Presynaptic maturation ................................................................................... 19 1.5.2.2 Synaptic vesicles and markers of presynaptic differentiation ......................... 20 1.5.2.3 Postsynaptic maturation ................................................................................. 22 1.5.2.4 Functional maturation of synapse ................................................................... 22 1.6 Morphological development and Regulation of Axonal mobility by KARs ................ 23 1.6.1 KARs in neurite outgrowth and morphological maturation of neurons ............ 23