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Journal article
Dynamic O-GlcNAc modification regulates CREB-mediated gene expression and memory formation
Nature chemical biology, v 8(3), pp 253-261
01 Mar 2012
PMID: 22267118
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The transcription factor cyclic AMP-response element binding protein (CREB) is a key regulator of many neuronal processes, including brain development, circadian rhythm and long-term memory. Studies of CREB have focused on its phosphorylation, although the diversity of CREB functions in the brain suggests additional forms of regulation. Here we expand on a chemoenzymatic strategy for quantifying glycosylation stoichiometries to characterize the functional roles of CREB glycosylation in neurons. We show that CREB is dynamically modified with an O-linked beta-N-acetyl-D-glucosamine sugar in response to neuronal activity and that glycosylation represses CREB-dependent transcription by impairing its association with CREB-regulated transcription coactivator (CRTC; also known as transducer of regulated CREB activity). Blocking glycosylation of CREB alters cellular function and behavioral plasticity, enhancing both axonal and dendritic growth and long-term memory consolidation. Our findings demonstrate a new role for O-glycosylation in memory formation and provide a mechanistic understanding of how glycosylation contributes to critical neuronal functions. Moreover, we identify a previously unknown mechanism for the regulation of activity-dependent gene expression, neural development and memory.
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Details
- Title
- Dynamic O-GlcNAc modification regulates CREB-mediated gene expression and memory formation
- Creators
- Jessica E. Rexach - California Institute of TechnologyPeter M. Clark - Howard Hughes Medical InstituteDaniel E. Mason - Genomics Institute of the Novartis Research FoundationRachael L. Neve - Picower Institute for Learning and MemoryEric C. Peters - Genomics Institute of the Novartis Research FoundationLinda C. Hsieh-Wilson - Howard Hughes Medical Institute
- Publication Details
- Nature chemical biology, v 8(3), pp 253-261
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- R01 GM084724; F31 NS056525; 5T32 GM07737 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM084724 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) F31NS056525 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000300600000010
- Scopus ID
- 2-s2.0-84857193629
- Other Identifier
- 991019356496204721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology