Work

PKCε Inhibits Neuronal Dendritic Spine Development through Dual Phosphorylation of Ephexin5

Year: 2018

Type: article

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.

Source: Cell Reports

DOI: 10.1016/j.celrep.2018.11.005

Authors: Thomas B. Schaffer, Jaclyn E. Smith, Emily K. Cook, Thao Phan, Seth S. Margolis

Institutions: Johns Hopkins University, Johns Hopkins Medicine

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,620

Funders: National Institutes of Health, National Science Foundation of Sri Lanka, National Institute of Mental Health, National Institute of General Medical Sciences