FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and De Novo GluA2 Translation
Denise Cook,
Erin Nuro,
Emma V. Jones,
Haider F. Altimimi,
W. Todd Farmer,
Valentina Gandin,
Edith Hanna,
Ruiting Zong,
Alessandro Barbon,
David L. Nelson,
Ivan Topisirovic,
Joseph Rochford,
David Stellwagen,
Jean-Claude Béïque,
Keith K. Murai
Affiliations
Denise Cook
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada
Erin Nuro
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada
Emma V. Jones
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada
Haider F. Altimimi
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada
W. Todd Farmer
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada
Valentina Gandin
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada
Edith Hanna
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada
Ruiting Zong
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Alessandro Barbon
Department of Molecular and Translational Medicine, National Institute of Neuroscience, University of Brescia, Brescia 25123, Italy
David L. Nelson
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Ivan Topisirovic
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada
Joseph Rochford
Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Verdun, QC H4H 1R3, Canada
David Stellwagen
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada
Jean-Claude Béïque
Department of Cellular and Molecular Medicine and Canadian Partnership for Stroke Recovery, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Keith K. Murai
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada
Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in nonneuronal cells and colocalizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase long-term potentiation (L-LTP), and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5′ UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 that is incorporated at potentiated synapses. This study uncovers a mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity.
