The CBP KIX domain regulates long-term memory and circadian activity

Snehajyoti Chatterjee; Christopher C Angelakos; Ethan Bahl; Joshua D Hawk; Marie E Gaine; Shane G Poplawski; Anne Schneider-Anthony; Manish Yadav; Giulia S Porcari; Jean-Christophe Cassel; K Peter Giese; Jacob J Michaelson; Lisa C Lyons; Anne-Laurence Boutillier; Ted Abel

doi:10.1186/s12915-020-00886-1

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The CBP KIX domain regulates long-term memory and circadian activity

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The CBP KIX domain regulates long-term memory and circadian activity

Snehajyoti Chatterjee, Christopher C Angelakos, Ethan Bahl, Joshua D Hawk, Marie E Gaine, Shane G Poplawski, Anne Schneider-Anthony, Manish Yadav, Giulia S Porcari, Jean-Christophe Cassel, …

BMC biology, Vol.18(1), pp.155-155

10/29/2020

DOI: 10.1186/s12915-020-00886-1

PMCID: PMC7597000

PMID: 33121486

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Abstract

CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors potentially affecting expression of thousands of genes. Identifying specific domain functions for multi-domain proteins is essential to understand processes such as cognitive function and circadian clocks. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBP mice with mutations that prevent phospho-CREB (Ser133) binding. We found that CBP mice were impaired in long-term memory, but not learning acquisition or short-term memory for the Morris water maze. Using an unbiased analysis of gene expression in the dorsal hippocampus after training in the Morris water maze or contextual fear conditioning, we discovered dysregulation of CREB, CLOCK, and BMAL1 target genes and downregulation of circadian genes in CBP mice. Given our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity and phase resetting in CBP mice. CBP mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark. Interestingly, CBP mice displayed phase delays and advances in response to photic stimulation comparable to wildtype littermates. Thus, this work delineates site-specific regulation of the circadian clock by a multi-domain protein. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.

Circadian rhythm

CBP KIX domain

Hippocampus

Spatial memory

Details

Title: Subtitle: The CBP KIX domain regulates long-term memory and circadian activity
Creators: Snehajyoti Chatterjee - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Christopher C Angelakos - Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
Ethan Bahl - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, USA
Joshua D Hawk - Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
Marie E Gaine - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Shane G Poplawski - Pharmacology Graduate Group, University of Pennsylvania, Philadelphia, USA
Anne Schneider-Anthony - LNCA, CNRS UMR 7364, Strasbourg, France
Manish Yadav - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Giulia S Porcari - Department of Biology, University of Pennsylvania, Philadelphia, PA, USA
Jean-Christophe Cassel - Laboratoire de Neuroscience Cognitives et Adaptatives (LNCA), Université de Strasbourg, Strasbourg, France
K Peter Giese - Department of Basic and Clinical Neuroscience, King's College London, London, UK
Jacob J Michaelson - Iowa Institute of Human Genetics, University of Iowa, Iowa City, Iowa, USA
Lisa C Lyons - Program in Neuroscience, Department of Biological Science, Florida State University, Tallahassee, FL, USA
Anne-Laurence Boutillier - LNCA, CNRS UMR 7364, Strasbourg, France. laurette@unistra.fr
Ted Abel - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. ted-abel@uiowa.edu
Resource Type: Journal article
Publication Details: BMC biology, Vol.18(1), pp.155-155
DOI: 10.1186/s12915-020-00886-1
PMID: 33121486
PMCID: PMC7597000
NLM abbreviation: BMC Biol
ISSN: 1741-7007
eISSN: 1741-7007
Publisher: England
Grant note: R01 MH087463 / NIMH NIH HHS 4803-3 / Indo-French Centre for the Promotion of Advanced Research
Language: English
Date published: 10/29/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065470202771

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