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

Shu Ling Chiu; Graham Hugh Diering; Bing Ye; Kogo Takamiya; Chih Ming Chen; Yuwu Jiang; Tejasvi Niranjan; Charles E. Schwartz; Tao Wang; Richard L. Huganir

doi:10.1016/j.neuron.2017.02.031

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

Shu Ling Chiu, Graham Hugh Diering, Bing Ye, Kogo Takamiya, Chih Ming Chen, Yuwu Jiang, Tejasvi Niranjan, Charles E. Schwartz, Tao Wang, Richard L. Huganir

School of Medicine

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1405-1419.e8
Journal	Neuron
Volume	93
Issue number	6
DOIs	https://doi.org/10.1016/j.neuron.2017.02.031
State	Published - Mar 22 2017

Keywords

GRIP1
glutamate receptor
glutamate uncaging
intellectual disability
long-term potentiation
neurodevelopmental disorder
neuronal connectivity
recycling endosomes
structural plasticity
syntaxin13

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/j.neuron.2017.02.031

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title = "GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors",

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.",

keywords = "GRIP1, glutamate receptor, glutamate uncaging, intellectual disability, long-term potentiation, neurodevelopmental disorder, neuronal connectivity, recycling endosomes, structural plasticity, syntaxin13",

author = "Chiu, {Shu Ling} and Diering, {Graham Hugh} and Bing Ye and Kogo Takamiya and Chen, {Chih Ming} and Yuwu Jiang and Tejasvi Niranjan and Schwartz, {Charles E.} and Tao Wang and Huganir, {Richard L.}",

note = "Funding Information: This work was supported by NIH grants NS36715 (R.L.H.), HD052680 (T.W.), and NS073854 (C.E.S.); the Brain and Behavior Research Foundation NARSAD Young Investigator Grant (19607) (S.-L.C.); and the Canadian Institute for Health Research postdoctoral fellowship award (G.H.D.). We thank Dr. Eric Gouaux for the GluA2 antibody; all members of the Huganir lab for helpful discussion and critical reading of the manuscript; and Drs. Lenora Volk, Se-Young Choi, Ingie Hong, Richard Roth, and Rebecca Rose for experimental support. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

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doi = "10.1016/j.neuron.2017.02.031",

language = "English (US)",

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AU - Chiu, Shu Ling

AU - Diering, Graham Hugh

AU - Ye, Bing

AU - Takamiya, Kogo

AU - Chen, Chih Ming

AU - Jiang, Yuwu

AU - Niranjan, Tejasvi

AU - Schwartz, Charles E.

AU - Wang, Tao

AU - Huganir, Richard L.

N1 - Funding Information: This work was supported by NIH grants NS36715 (R.L.H.), HD052680 (T.W.), and NS073854 (C.E.S.); the Brain and Behavior Research Foundation NARSAD Young Investigator Grant (19607) (S.-L.C.); and the Canadian Institute for Health Research postdoctoral fellowship award (G.H.D.). We thank Dr. Eric Gouaux for the GluA2 antibody; all members of the Huganir lab for helpful discussion and critical reading of the manuscript; and Drs. Lenora Volk, Se-Young Choi, Ingie Hong, Richard Roth, and Rebecca Rose for experimental support. Publisher Copyright: © 2017 Elsevier Inc.

PY - 2017/3/22

Y1 - 2017/3/22

N2 - 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.

AB - 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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ER -

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

Abstract

Keywords

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