Co-localization of hippocampal cholinergic neurostimulating peptide precursor with collapsin response mediator protein-2 at presynaptic terminals in hippocampus

► HCNP-pp co-localizes with CRMP-2 in all neuronal structures of the hippocampus. ► HCNP-pp binds to CRMP-2 in the hippocampus. ► HCNP-pp co-localizes with CRMP-2 at presynaptic terminals in the hippocampus. ► Overexpression of HCNP-pp increases both CRMP-2 and synaptophysin levels. Hippocampal cholinergic neurostimulating peptide (HCNP) induces the synthesis of acetylcholine in medial septal nucleus in vitro and in vivo. HCNP precursor protein (HCNP-pp) is a multifunctional protein that participates in a number of signaling pathways, including MAPK/extracellular signal and G-protein-coupled receptor kinase 2. We recently demonstrated that the amount of collapsin response mediator protein-2 (CRMP-2) is increased in hippocampus of HCNP-pp transgenic mice. To clarify the interaction between HCNP/HCNP-pp and CRMP-2 and its role in synaptic function, we investigated whether HCNP-pp is localized to the synapse and if it affects protein expression. Here, we demonstrate that HCNP-pp co-localizes with CRMP-2 at presynaptic terminals. Furthermore, HCNP-pp overexpression increases synaptophysin levels. These findings suggest that HCNP-pp, in association with CRMP-2, plays an important role in presynaptic function in the hippocampus.