SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex

Tankou, S. et al. (2016) SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex. Molecular Neuropsychiatry, 2(1), pp. 20-27. (doi: 10.1159/000444257) (PMID:27525255) (PMCID:PMC4979612)

Abstract

DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy between modest evidence in genetics and strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions. In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Elliott, Dr Christina and Baillie, Professor George and Houslay, Professor Miles and Yalla, Dr Krishna
• Authors: Tankou, S., Ishii, K., Elliott, C., Yalla, K., Kubo, K.-i., Brandon, N. J., Tang, Q., Hayward, G., Nakajima, K., Houslay, M., Kamiya, A., Baillie, G., Ishizuka, K., and Sawa, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Molecular Neuropsychiatry
• Publisher: Karger
• ISSN: 2296-9209
• ISSN (Online): 2296-9179
• Published Online: 15 March 2016
• Copyright Holders: Copyright © 2016 S. Karger AG, Basel
• First Published: First published in Molecular Neuropsychiatry 2(1):20-27
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher