Feline Lindhout

152 5 Figure 1. Updated views on molecular processes underlying axon formation and functioning A. Centrosomes display microtubule-organizing center (MTOC) functions at early stages 1 and 2, which coincides with local presence of Trim46 proteins ( I ). The MTOC functions of centrosomes are markedly declined in stage 3a neurons ( II ), and transform into cilia during further neuronal maturation ( III ). B,C. The transformation of a non-polarized neurite in a stage 2 neuron ( I ) into an axon in a stage 3 neuron ( II and III ) involves the reorganization of the microtubule (MT) cytoskeleton from a mixed to uniform plus-end out orientation, as well as the accumulation and assembly of axon initial segment (AIS) proteins (e.g. Trim46 and AnkyrinG). All these developmental processes occur first at distal axons ( C ) in stage 3a neurons ( II ), followed by rearrangements at proximal axons ( B ) in stage 3b neurons ( III ). D. Neurotransmitter (NT) release at presynaptic sites of mature axons ( III ) is mediated by the synaptic vesicle cycle, involving the local Ca 2+ -driven exocytosis and subsequent retrieval of synaptic vesicles (SVs). The dynamic ER structure plays an important role in synaptic vesicle recycling, which is mediated by molecular interactions between VAP proteins and VAP-interacting protein Secernin-1 (SCRN1).