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Publication

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

Neuron | 2017

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.

Pubmed ID: 28285821 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

MacVector (RRID:SCR_015700)

Antibodies used in this publication

Associated grants

Agency: NINDS NIH HHS, United States
Id: P30 NS050274
Agency: NIMH NIH HHS, United States
Id: R01 MH112151
Agency: NIA NIH HHS, United States
Id: P50 AG005146
Agency: NINDS NIH HHS, United States
Id: R01 NS036715
Agency: NIMH NIH HHS, United States
Id: R01 MH112808
Agency: NINDS NIH HHS, United States
Id: R01 NS073854

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This is a list of tools and resources that we have found mentioned in this publication.

MacVector (tool)

RRID:SCR_015700

Software application that provides sequence editing, primer design, internet database searching, protein analysis, sequence confirmation, multiple sequence alignment, phylogenetic reconstruction, coding region analysis, agarose gel simulation and a variety of other functions.

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Anti-PSD-95 Antibody (antibody)

RRID:AB_2292909

This monoclonal targets PSD 95

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Anti-Syntaxin 11 (antibody)

RRID:AB_10639254

This polyclonal targets Syntaxin 11

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Rabbit Anti-Mouse Protein Interacting With PRKCA 1 (PICK1) Polyclonal, Unconjugated (antibody)

RRID:AB_1934342

This polyclonal targets Mouse Protein Interacting With PRKCA 1 (PICK1)

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Anti-GRIP1 (RABBIT) Antibody - 600-401-BP2 (antibody)

RRID:AB_2613149

This unknown targets GRIP1 Antibody

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GRASP1 antibody [N3], Internal (antibody)

RRID:AB_10723427

This polyclonal targets GRASP1

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Monoclonal Anti-alpha-Tubulin antibody produced in mouse (antibody)

RRID:AB_477582

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Rabbit Anti-Metabotropic Glutamate Receptor 5 Monoclonal Antibody, Unconjugated, Clone EPR2425Y (antibody)

RRID:AB_1523944

This monoclonal targets Metabotropic Glutamate Receptor 5

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Mouse Anti-Rab4 Monoclonal Antibody, Unconjugated, Clone 7 (antibody)

RRID:AB_398206

This monoclonal targets Rab4

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GRIP (antibody)

RRID:AB_398845

This monoclonal targets GRIP

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Influenza hemagglutinin epitope (YPYDVPDYA) (antibody)

RRID:AB_2314672

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Living Colors® DsRed Polyclonal Antibody (antibody)

RRID:AB_10013483

This polyclonal targets DsRed

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Anti-Green Fluorescent Protein Antibody (antibody)

RRID:AB_10000240

This polyclonal targets Green Fluorescent Protein (GFP)

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GFP (18A11) (antibody)

RRID:AB_1123603

This monoclonal targets GFP (18A11)

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LAMP1 antibody (antibody)

RRID:AB_2134489

This polyclonal targets Lamp1

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Rabbit Anti-EEA1 Monoclonal Antibody, Unconjugated, Clone C45B10 (antibody)

RRID:AB_2096811

This monoclonal targets EEA1

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Anti-Syntaxin 12/13 (antibody)

RRID:AB_887845

This polyclonal targets Syntaxin 12/13

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Anti-Syntaxin 12/13 (antibody)

RRID:AB_2198225

This polyclonal targets Syntaxin 12/13

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FUGW-H1-GFP-neomycin (plasmid)

RRID:Addgene_37632

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ScanImage (software resource)

RRID:SCR_014307

Open source software application for laser scanning microscopy, electrophysiology, laser scanning photostimulation, and other physiological methods focused on neurobiology. Used to control laser scanning microscopes without need for custom data acquisition hardware. Standard data acquisition boards are used to acquire data and control laser scanning. The tasks of signal integration and image processing are placed on the computer CPU. Multiple versions of ScanImage are available, each with their own features.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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MetaMorph Microscopy Automation and Image Analysis Software (software resource)

RRID:SCR_002368

Software tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.

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