Format

Send to

Choose Destination
Mol Cell Neurosci. 2015 Mar;65:52-7. doi: 10.1016/j.mcn.2015.02.010. Epub 2015 Feb 19.

Synaptic structure and function are altered by the neddylation inhibitor MLN4924.

Author information

1
Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, United States. Electronic address: sscudder@ucsd.edu.
2
Section of Neurobiology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, United States. Electronic address: gpatrick@ucsd.edu.

Abstract

The posttranslational modification of proteins by the ubiquitin-like small molecule NEDD8 has previously been shown to be vital in a number of cell signaling pathways. In particular, conjugation of NEDD8 (neddylation) serves to regulate protein ubiquitination through modifications to E3 ubiquitin ligases. Despite the prevalence of NEDD8 in neurons, very little work has been done to characterize the role of this modifier in these cells. Here, we use the recently developed NEDD8 Activating Enzyme (NAE) inhibitor MLN4924 and report evidence of a role for NEDD8 in regulating mammalian excitatory synapses. Application of this drug to dissociated rat hippocampal neurons caused reductions in synaptic strength, surface glutamate receptor levels, dendritic spine width, and spine density, suggesting that neddylation is involved in the maintenance of synapses.

KEYWORDS:

Hippocampus; MLN4924; NEDD8; Synapse; Ubiquitin

PMID:
25701678
PMCID:
PMC4844066
DOI:
10.1016/j.mcn.2015.02.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center