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

Protein kinase C mechanisms promote synaptic function in the mature brain. However, the roles of signaling during synapse development remain largely unknown. Investigating each brain-enriched duanyu1531 isoform in early neuronal development, we show that acutely and specifically reduces the number of dendritic spines, sites of eventual synapse formation on developing dendrites. This 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 duanyu1531ε 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 Ephexin5, whose early-elevated expression in developing neurons may in part explain the mechanism by which duanyu1531ε plays seemingly opposing roles that depend on neuronal maturity.

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