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Cited by 66Neuroscience and Neuropharmacology ResearchCellular transport and secretionGenetics and Neurodevelopmental Disorders

GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors

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Chiu, Shu-Ling, Diering, Graham Hugh, Ye, Bing, Takamiya, Kogo, Chen, Chih-Ming, Jiang, Yuwu, Niranjan, Tejasvi, Schwartz, Charles E. +2 more·2017·Neuron
DOI 10.1016/j.neuron.2017.02.031PMC PMC5382714
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Abstract

Learning depends on experience-dependent modification of synaptic efficacy and neuronal connectivity in the brain. We provide direct evidence for physiological roles of the recycling endosome protein GRASP1 in glutamatergic synapse function and animal behavior. Mice lacking GRASP1 showed abnormal excitatory synapse number, synaptic plasticity, and hippocampal-dependent learning and memory due to a failure in learning-induced synaptic AMPAR incorporation. We identified two GRASP1 point mutations from intellectual disability (ID) patients that showed convergent disruptive effects on AMPAR recycling and glutamate uncaging-induced structural and functional plasticity. Wild-type GRASP1, but not ID mutants, rescued spine loss in hippocampal CA1 neurons in Grasp1 knockout mice. Together, these results demonstrate a requirement for normal recycling endosome function in AMPAR-dependent synaptic function and neuronal connectivity in vivo, and suggest a potential role for GRASP1 in the pathophysiology of human cognitive disorders.

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  • Mice lacking PICK1, KIBRA or Grasp1 all show reductions in hippocampal LTP as well as defects in hippocampus-dependent learning and memory tasks.

    “Mice lacking PICK1, KIBRA or Grasp1 all show reductions in hippocampal LTP as well as defects in hippocampus-dependent learning and memory tasks (Makuch et al., 2011, Volk et al., 2010, Chiu et al., 2017)”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Chiu et al., 2017

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Authors
Chiu, S.-L., Diering, G. H., Ye, B., Takamiya, K., Chen, C.-M., Jiang, Y., Niranjan, T., Schwartz, C. E., Wang, T., & Huganir, R. L.
Affiliations
  • Johns Hopkins University (US)
  • University of Miyazaki (JP)
  • Greenwood Genetic Center (US)
Corresponding author
Huganir, Richard L.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2017-03
Volume
93
Issue
6
Pages
1405-1419.e8
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2017.02.031
PMC
PMC5382714
OpenAlex
W2593299310
Cited by
66
References
7
Citations by year
2026: 4 · 2025: 8 · 2024: 11 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 4 · 2018: 10 · 2017: 3
FWCI
3.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Brain and Behavior Research Foundation (19607)
  • Canadian Institutes of Health Research
  • National Institutes of Health (HD052680, NS073854, NS36715)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
recycling endosomes, AMPA receptor trafficking, synaptic plasticity, hippocampal-dependent learning and memory, intellectual disability, glutamatergic synapses, spine loss, glutamate uncaging, cognitive disorders
MeSH terms
Animals, Avoidance Learning, Carrier Proteins, Cells, Cultured, Humans, Learning, Male, Intellectual Disability, Mutation, Neuronal Plasticity, Endosomes, Synapses, Case-Control Studies, Receptors, AMPA, Mice, Knockout, Glutamic Acid, Maze Learning, Mice, CA1 Region, Hippocampal

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