Edinburgh Research Explorer

Neurobeachin Regulates Glutamate- and GABA-Receptor Targeting to Synapses via Distinct Pathways

Research output: Contribution to journalArticle

  • F. Farzana
  • R. Zalm
  • N. Chen
  • K. W. Li
  • Seth G N Grant
  • A. B. Smit
  • R. F. Toonen
  • M. Verhage

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Rights statement: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

    Final published version, 1 MB, PDF document

    Licence: Creative Commons: Attribution (CC-BY)

Original languageEnglish
Pages (from-to)2112-2123
Number of pages12
JournalMolecular Neurobiology
Volume53
Issue number4
DOIs
Publication statusPublished - 2 May 2016

Abstract

Neurotransmission and synaptic strength depend on expression of post-synaptic receptors on the cell surface. Post-translational modification of receptors, trafficking to the synapse through the secretory pathway, and subsequent insertion into the synapse involves interaction of the receptor with A-kinase anchor proteins (AKAPs) and scaffolding proteins. Neurobeachin (Nbea), a brain specific AKAP, is required for synaptic surface expression of both glutamate and GABA receptors. Here, we investigated the role of Nbea-dependent targeting of postsynaptic receptors by studying Nbea interaction with synapse-associated protein 102 (SAP102/Dlg3) and protein kinase A subunit II (PKA II). A Nbea mutant lacking the PKA binding domain showed a similar distribution as wild-type Nbea in Nbea null neurons and partially restored GABA receptor surface expression. To understand the relevance of Nbea interaction with SAP102, we analysed SAP102 null mutant mice. Nbea levels were reduced by ~80 % in SAP102 null mice, but glutamatergic receptor expression was normal. A single-point mutation in the pleckstrin homology domain of Nbea (E2218R) resulted in loss of binding with SAP102. When expressed in Nbea null neurons, this mutant fully restored GABA receptor surface expression, but not glutamate receptor expression. Our results suggest that the PKA-binding domain is not essential for Nbea’s role in receptor targeting and that Nbea targets glutamate and GABA receptors to the synapse via distinct molecular pathways by interacting with specific effector proteins.

    Research areas

  • AKAP, GABA receptors, Glutamate receptors, Neurobeachin, SAP102, Synapse

Download statistics

No data available

ID: 25329884