Dense core vesicle transport and synaptic capture in neurons

Dense core vesicles (DCVs) transport signalling molecules, such as brain-derived neurotrophic factor (BDNF), to neuronal synapses utilizing the kinesin KIF1A. BDNF is critical for neuronal function, therefore it is important to understand DCV trafficking and synaptic capture. I used live-cell imaging to characterize DCVs carrying fluorescently tagged BDNF in hippocampal neurons to assess how they translocate to presynaptic sites. Transport was processive both anterogradely and retrogradely and DCVs can be captured regardless of the direction in which they are traveling. Next, I studied whether absence of doublecortin-like kinase 1 (DCLK1), a KIF1A motility modulator, allows for DCV capture at synapses. Using super-resolution microscopy, DCLK1 co-localized only with a small fraction of axonal DCVs. Despite low co-localization of DCLK1 and DCVs, DCLK1 was absent from most synapses (64%). These observations suggest that DCLK1 may not regulate DCV transport in axons but may regulate movement of other KIF1A cargo.