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PKCε Inhibits Neuronal Dendritic Spine Development through Dual Phosphorylation of Ephexin5.

Cell reports | 2018

Protein kinase C (PKC)-dependent mechanisms promote synaptic function in the mature brain. However, the roles of PKC signaling during synapse development remain largely unknown. Investigating each brain-enriched PKC isoform in early neuronal development, we show that PKCε acutely and specifically reduces the number of dendritic spines, sites of eventual synapse formation on developing dendrites. This PKCε-mediated spine suppression is temporally restricted to immature neurons and mediated through the phosphorylation and activation of Ephexin5, a RhoA guanine nucleotide exchange factor (GEF) and inhibitor of hippocampal synapse formation. Our data suggest that PKCε acts as an early developmental inhibitor of dendritic spine formation, in contrast to its emerging pro-synaptic roles in mature brain function. Moreover, we identify a substrate of PKCε, Ephexin5, whose early-elevated expression in developing neurons may in part explain the mechanism by which PKCε plays seemingly opposing roles that depend on neuronal maturity.

Pubmed ID: 30485813 RIS Download

Research resources used in this publication

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH102364
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007445

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