Dataset Information

A Noelin-organized extracellular network of proteins required for constitutive and context-dependent anchoring of AMPA-receptors

ABSTRACT: Information processing and storage in the brain rely on AMPA-receptors (AMPARs) and their context-dependent dynamics in synapses and extra-synaptic sites. We found that distribution and dynamics of AMPARs in the plasma membrane are controlled by Noelins, a three-member family of conserved secreted proteins expressed throughout the brain in a cell type-specific manner. Noelin tetramers tightly assemble with the extracellular domains of AMPARs and interconnect them in a network-like configuration with a variety of secreted and membrane-anchored proteins including Neurexin1, Neuritin1, and Seizure 6-like. Knockout of Noelins1-3 profoundly reduced AMPARs in synapses onto excitatory and inhibitory (inter)neurons, decreased their density and clustering in dendrites and abolished activity-dependent synaptic plasticity. Our results uncover an endogenous mechanism for extracellular anchoring of AMPARs and establish Noelin-organized networks as versatile determinants of constitutive and context-dependent neurotransmission.

INSTRUMENT(S): LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Rattus Norvegicus (rat) Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Alexander Haupt

LAB HEAD: Prof. Dr. Bernd Fakler

PROVIDER: PXD041655 | Pride | 2024-03-13

REPOSITORIES: Pride

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A Noelin-organized extracellular network of proteins required for constitutive and context-dependent anchoring of AMPA-receptors.

Boudkkazi Sami S Schwenk Jochen J Nakaya Naoki N Brechet Aline A Kollewe Astrid A Harada Harumi H Bildl Wolfgang W Kulik Akos A Dong Lijin L Sultana Afia A Zolles Gerd G Schulte Uwe U Tomarev Stanislav S Fakler Bernd B

Neuron 20230801 16

Information processing and storage in the brain rely on AMPA-receptors (AMPARs) and their context-dependent dynamics in synapses and extra-synaptic sites. We found that distribution and dynamics of AMPARs in the plasma membrane are controlled by Noelins, a three-member family of conserved secreted proteins expressed throughout the brain in a cell-type-specific manner. Noelin tetramers tightly assemble with the extracellular domains of AMPARs and interconnect them in a network-like configuration ...[more]

PMID: 37591201

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