Site‐Specific Phosphorylation of Neurofilament‐L Is Mediated by Calcium/Calmodulin‐Dependent Protein Kinase II in the Apical Dendrites During Long‐Term Potentiation

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Abstract
: Neurofilament‐L (NF‐L), one subunit of the neuronal intermediate filaments, is a major element of neuronal cytoskeletons. The dynamics of NF‐L are regulated by phosphorylation of its head domain. The phosphorylation sites of the NF‐L head domain by protein kinase A, protein kinase C, and Rho‐associated kinase have been previously identified, and those by calcium/calmodulin‐dependent protein kinase II (CaMKII) were identified in this study. A series of site‐ and phosphorylation state‐specific antibodies against NF‐L was prepared to investigate NF‐L phosphorylation in neuronal systems. Long‐term potentiation (LTP) is a cellular model of neuronal plasticity that is thought to involve the phosphorylation of various proteins. NF‐L is considered a possible substrate for phosphorylation. During LTP stimulation of mouse hippocampal slices, the series of antibodies demonstrated the increase in the phosphorylation level of Ser57 in NF‐L and the visualization of the localized distribution of Ser57 phosphorylation in a subpopulation of apical dendrites of the pyramidal neurons. Furthermore, Ser57 phosphorylation during LTP is suggested to be mediated by CaMKII. Here we show that NF‐L is phosphorylated by CaMKII in a subpopulation of apical dendrites during LTP, indicating that Ser57 is a novel phosphorylation site of NF‐L in vivo related to the neuronal signal transduction.