TY - JOUR
T1 - SUMOylation of DISC1
T2 - A Potential Role in Neural Progenitor Proliferation in the Developing Cortex
AU - Tankou, Stephanie
AU - Ishii, Kazuhiro
AU - Elliott, Christina
AU - Yalla, Krishna C.
AU - Day, Jon P.
AU - Furukori, Keiko
AU - Kubo, Ken-ichiro
AU - Brandon, Nicholas J.
AU - Tang, Qiyi
AU - Hayward, Gary
AU - Nakajima, Kazunori
AU - Houslay, Miles D.
AU - Kamiya, Atsushi
AU - Baillie, George S.
AU - Ishizuka, Koko
AU - Sawa, Akira
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
U2 - 10.1159/000444257
DO - 10.1159/000444257
M3 - Article
SN - 2296-9209
VL - 2
SP - 20
EP - 27
JO - Molecular Neuropsychiatry
JF - Molecular Neuropsychiatry
IS - 1
ER -