Site-specific dephosphorylation of doublecortin (DCX) by protein phosphatase 1 (PP1)

Molecular and Cellular Neurosciences
Anat ShmueliO Reiner

Abstract

Mutations in doublecortin (DCX) cause X-linked lissencephaly ("smooth brain") and double cortex syndrome in humans. DCX is highly phosphorylated in migrating neurons. Here, we demonstrate that dephosphorylation of specific sites phosphorylated by JNK is mediated by Neurabin II, which recruits the phosphatase PP1. During cortical development, the expression pattern of PP1 is widespread, while the expression of DCX and Neurabin II is dynamic, and they are coexpressed in migrating neurons. In vitro, DCX is site-specific dephosphorylated by PP1 without the presence of Neurabin II, this dephosphorylation requires an intact RVXF motif in DCX. Overexpression of the coiled-coil domain of Neurabin II, which is sufficient for interacting with DCX and recruiting the endogenous Neurabin II with PP1, induced dephosphorylation of DCX on one of the JNK-phosphorylated sites. We hypothesize that the transient recruitment of DCX to different scaffold proteins, JIP-1/2, which will regulate its phosphorylation by JNK, and Neurabin II, which will regulate its dephosphorylation by PP1, plays an important role in normal neuronal migration.

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Citations

Mar 31, 2009·Molecular Neurobiology·Orly Reiner, Tamar Sapir
Sep 4, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Irina TintMark M Black
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Aug 28, 2021·International Journal of Molecular Sciences·Béatrice BenoitChristian Poüs

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