title: Phosphorylation of collapsin response mediator protein-2 regulates its localization and association with hippocampal cholinergic neurostimulating peptide precursor in the hippocampus.
abstract: Hippocampal cholinergic neurostimulating peptide (HCNP) induces the synthesis of acetylcholine in the medial septal nucleus in vitro and in vivo. The precursor, HCNP-pp, is a multifunctional protein participating in important signaling pathways, such as MAPK/ERK kinase (MEK) and G-protein-coupled receptor kinase 2 (GRK2). We recently demonstrated that HCNP-pp colocalizes with collapsin response mediator protein-2 (CRMP-2) at presynaptic terminals in the hippocampus, suggesting that HCNP-pp may play an important role in presynaptic function in association with CRMP-2. To clarify the involvement of phosphorylation in regulating the interaction between HCNP-pp and CRMP-2, we investigated the colocalization of HCNP-pp with unphosphorylated- and/or phosphorylated-CRMP-2 (pCRMP-2) at presynaptic terminals. We further determined if the phosphorylation of CRMP-2 affects the binding between those proteins. Here, we demonstrate that HCNP-pp predominantly colocalizes and associates with unphosphorylated and/or pSer-522-CRMP-2 at presynaptic terminals in the hippocampus. Interestingly, HCNP-pp does not associate with pThr-509/514-CRMP-2, which is primarily localized at postsynaptic terminals. These findings suggest that HCNP-pp, in association with unphosphorylated and/or pSer522-CRMP-2, plays an important role in presynaptic function in the mature hippocampus.
authors.affiliation: Department of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mizuno
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kato
authors.forename: Tetsuko
authors.initials: T
authors.lastname: Kanamori
authors.forename: Takanari
authors.initials: T
authors.lastname: Toyoda
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kosei
authors.initials: K
authors.lastname: Ojika
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Matsukawa
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D049488:Phosphatidylethanolamine Binding Protein; C095114:collapsin response mediator protein-2