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Regulation of neural cell adhesion molecule polysialylation state by cell‐cell contact and protein kinase C delta
Author(s) -
Gallagher Helen C.,
Odumeru Oladapo A.,
Regan Ciaran M.
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20000915)61:6<636::aid-jnr7>3.0.co;2-f
Subject(s) - neural cell adhesion molecule , polysialic acid , protein kinase c , staurosporine , chemistry , microbiology and biotechnology , cell adhesion , cell , signal transduction , biology , biochemistry
Post‐translational modification of neural cell adhesion molecule (NCAM) with α2,8‐linked polysialic acid, which regulates homophilic adhesion and/or signal transduction events, is crucial to synaptic plasticity in the developing and adult brain. Evidence from in vitro models has implicated polysialylation in the regulation of cell growth, migration, and differentiation. Here, using two in vitro models, we demonstrate that polysialylation is downregulated by cell‐cell contact and correlated with a state of neuronal differentiation. Furthermore, we report a role for protein kinase C delta (PKCδ) in the regulation of NCAM polysialylation. Pharmacological studies using the PKC activator, phorbol myristate acetate, and inhibitors, calphostin‐C, and staurosporine, demonstrated PKC activity to be inversely related to NCAM polysialylation in the mouse neuro‐2A cell line. Isoform‐specific immunoblot studies indicated this effect to be mediated by the calcium‐independent PKCδ isozyme, as its expression was inversely related to NCAM polysialylation state in both neuro‐2A and rat PC‐12 cell lines. Isoform specificity was further confirmed using the PKCδ‐selective inhibitor rottlerin, which produced a marked increase in PSA expression (36.9 ± 5.25 a.u. vs. 24.7 ± 0.80 arbitrary units control) coupled with a neuritogenic response. Likewise, decreased expression of PKCδ was seen in nerve growth factor (NGF)‐differentiated PC‐12 cells. These findings suggest that the neuronal differentiation process may involve inhibition of PKCδ, resulting in enhanced morphological plasticity, as evidenced by activation of NCAM polysialylation. J. Neurosci. Res. 61:636–645, 2000. © 2000 Wiley‐Liss, Inc.