KIF1A: a candidate motor protein for dense-core vesicle transport in cultured hippocampal neurons

Axonal transport of membrane bound organelles is essential for neuronal cell function and survival. Dense-core vesicles (DCVs) are cargo-carrying organelles in neurons responsible for transporting and secreting neuropeptides such as brain derived neurotrophic factor (BDNF). DCVs are synthesized in the cell body and travel large distances on microtubules to pre- and postsynaptic release sites. This thesis sought to determine if the Kinesin-3 family member KIF1A transports DCVs in primary cultured hippocampal neurons. This was done by reducing KIF1A protein expression in neurons through RNA interference and imaging the movement of DCV marker BDNF-RFP in experimental and control cells. Two-colour live-cell imaging of BDNF-RFP and KIF1A-GFP was preformed to establish an association between KIF1A and DCVs. Cells in which KIF1A was reduced showed a marked decrease in overall DCV flux compared to control cells. This data supports a primary role for KIF1A in the anterograde transport of DCVs in mammalian neurons.