Feline Lindhout

1 General introduction 19 Figure 2. The synaptic vesicle cycle A schematic illustration of a synaptic contact formed between the axon and a dendrite of different neurons. The zoom represents a detailed overview of a synapse composed of a presynaptic site present at the axon, a postsynaptic site present at a dendrite, and a synaptic cleft in between. The presynaptic site is populated by synaptic vesicles containing neurotransmitters as well as specialized structures, such as the presynaptic endoplasmic reticulum (ER) network. When an action potential is present at a presynaptic site, voltage-gated Ca 2+ channels will open. This results in a Ca 2+ influx that drives the endocytosis of neurotransmitter-containing synaptic vesicles at the presynaptic membrane. The neurotransmitters are released in the synaptic cleft and bind to the postsynaptic receptors. Meanwhile, the synaptic vesicle membrane is recycled from the presynaptic membrane and refilled with neurotransmitters to replenish the local pool of neurotransmitter-containing synaptic vesicles. The role of the dynamic presynaptic ER structure during this highly coordinated process of synaptic vesicle recycling remains elusive. and carefully selected model systems. The work in this thesis provides new insights in cytoskeletal-mediated mechanisms that underlie axon formation in human neurons, which marks one of the first steps in establishing neuronal polarity. By focusing on the functioning