PKCε Inhibits Neuronal Dendritic Spine Development Through Dual Phosphorylation of Ephexin5

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Nov 29

PMID 30485813

Citations 9

Authors

Thomas B Schaffer

Jaclyn E Smith

Emily K Cook

Thao Phan

Seth S Margolis

Affiliations

Soon will be listed here.

Abstract

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.

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