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Neural Plasticity
Volume 2012 (2012), Article ID 892749, 13 pages
Review Article

The Role of Deubiquitinating Enzymes in Synaptic Function and Nervous System Diseases

1Department of Biological Sciences, Butler University, 4600 Sunset Avenue, Indianapolis, IN 46208, USA
2Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA

Received 19 September 2012; Accepted 25 November 2012

Academic Editor: Yuji Ikegaya

Copyright © 2012 Jennifer R. Kowalski and Peter Juo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Posttranslational modification of proteins by ubiquitin has emerged as a critical regulator of synapse development and function. Ubiquitination is a reversible modification mediated by the concerted action of a large number of specific ubiquitin ligases and ubiquitin proteases, called deubiquitinating enzymes (DUBs). The balance of activity of these enzymes determines the localization, function, and stability of target proteins. While some DUBs counter the action of specific ubiquitin ligases by removing ubiquitin and editing ubiquitin chains, other DUBs function more generally to maintain the cellular pool of free ubiquitin monomers. The importance of DUB function at the synapse is underscored by the association of specific mutations in DUB genes with several neurological disorders. Over the last decade, although much research has led to the identification and characterization of many ubiquitin ligases at the synapse, our knowledge of the relevant DUBs that act at the synapse has lagged. This review is focused on highlighting our current understanding of DUBs that regulate synaptic function and the diseases that result from dysfunction of these DUBs.