Small ubiquitin-like modifier 2 (SUMO2) is critical for memory processes in mice.

Yu, Shu

Galeffi, Francesca

Rodriguiz, Ramona M

Wang, Zhuoran

Shen, Yuntian

Lyu, Jingjun

Li, Ran

Bernstock, Joshua D

Johnson, Kory R

Liu, Shuai

Sheng, Huaxin

Turner, Dennis A

Wetsel, William C

Paschen, Wulf

Yang, Wei

2021-06-01T13:41:28Z

2021-06-01T13:41:28Z

2020-11

2021-06-01T13:41:27Z

Small ubiquitin-like modifier (SUMO1-3) conjugation (SUMOylation), a posttranslational modification, modulates almost all major cellular processes. Mounting evidence indicates that SUMOylation plays a crucial role in maintaining and regulating neural function, and importantly its dysfunction is implicated in cognitive impairment in humans. We have previously shown that simultaneously silencing SUMO1-3 expression in neurons negatively affects cognitive function. However, the roles of the individual SUMOs in modulating cognition and the mechanisms that link SUMOylation to cognitive processes remain unknown. To address these questions, in this study, we have focused on SUMO2 and generated a new conditional Sumo2 knockout mouse line. We found that conditional deletion of Sumo2 predominantly in forebrain neurons resulted in marked impairments in various cognitive tests, including episodic and fear memory. Our data further suggest that these abnormalities are attributable neither to constitutive changes in gene expression nor to alterations in neuronal morphology, but they involve impairment in dynamic SUMOylation processes associated with synaptic plasticity. Finally, we provide evidence that dysfunction on hippocampal-based cognitive tasks was associated with a significant deficit in the maintenance of hippocampal long-term potentiation in Sumo2 knockout mice. Collectively, these data demonstrate that protein conjugation by SUMO2 is critically involved in cognitive processes.

0892-6638

1530-6860

https://hdl.handle.net/10161/23238

eng

Wiley

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

10.1096/fj.202000850rr

Hippocampus

Prosencephalon

Animals

Mice, Inbred C57BL

Mice

Small Ubiquitin-Related Modifier Proteins

Cognition

Memory

Long-Term Potentiation

Female

Male

Small ubiquitin-like modifier 2 (SUMO2) is critical for memory processes in mice.

Journal article

Sheng, Huaxin|0000-0002-4325-2940

Turner, Dennis A|0000-0001-7118-0764

Yang, Wei|0000-0001-5719-4393

14750

14767

11

School of Medicine

Anesthesiology

Duke

Clinical Science Departments

Biomedical Engineering

Neurobiology

Duke Institute for Brain Sciences

Orthopaedics

Neurosurgery

Pratt School of Engineering

Basic Science Departments

University Institutes and Centers

Institutes and Provost's Academic Units

Cell Biology

Psychiatry & Behavioral Sciences, Translational Neuroscience

Medicine, Endocrinology, Metabolism, and Nutrition

Psychiatry & Behavioral Sciences

Medicine

Published

34