Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling

Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling

Neuregulin 1 (NRG1) and the γ-secretase subunit APH1B have been previously implicated as genetic risk factors for schizophrenia and schizophrenia relevant deficits have been observed in rodent models with loss of function mutations in either gene. Here we show that the Aph1b-γ-secretase is selective...

Full description

Bibliographic Details
Main Authors: Fazzari, Pietro, Snellinx, An, Sabanov, Victor, Ahmed, Tariq, Serneels, Lutgarde, Gartner, Annette, Shariati, S Ali M, Balschun, Detlef, De Strooper, Bart
Format: Online
Language:English
Published: eLife Sciences Publications, Ltd 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073283/
id pubmed-4073283
recordtype oai_dc
spelling pubmed-40732832014-07-22 Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling Fazzari, Pietro Snellinx, An Sabanov, Victor Ahmed, Tariq Serneels, Lutgarde Gartner, Annette Shariati, S Ali M Balschun, Detlef De Strooper, Bart Neuroscience Neuregulin 1 (NRG1) and the γ-secretase subunit APH1B have been previously implicated as genetic risk factors for schizophrenia and schizophrenia relevant deficits have been observed in rodent models with loss of function mutations in either gene. Here we show that the Aph1b-γ-secretase is selectively involved in Nrg1 intracellular signalling. We found that Aph1b-deficient mice display a decrease in excitatory synaptic markers. Electrophysiological recordings show that Aph1b is required for excitatory synaptic transmission and plasticity. Furthermore, gain and loss of function and genetic rescue experiments indicate that Nrg1 intracellular signalling promotes dendritic spine formation downstream of Aph1b-γ-secretase in vitro and in vivo. In conclusion, our study sheds light on the physiological role of Aph1b-γ-secretase in brain and provides a new mechanistic perspective on the relevance of NRG1 processing in schizophrenia. eLife Sciences Publications, Ltd 2014-06-02 /pmc/articles/PMC4073283/ /pubmed/24891237 http://dx.doi.org/10.7554/eLife.02196 Text en Copyright © 2014, Fazzari et al http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Fazzari, Pietro
Snellinx, An
Sabanov, Victor
Ahmed, Tariq
Serneels, Lutgarde
Gartner, Annette
Shariati, S Ali M
Balschun, Detlef
De Strooper, Bart
spellingShingle Fazzari, Pietro
Snellinx, An
Sabanov, Victor
Ahmed, Tariq
Serneels, Lutgarde
Gartner, Annette
Shariati, S Ali M
Balschun, Detlef
De Strooper, Bart
Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling
author_facet Fazzari, Pietro
Snellinx, An
Sabanov, Victor
Ahmed, Tariq
Serneels, Lutgarde
Gartner, Annette
Shariati, S Ali M
Balschun, Detlef
De Strooper, Bart
author_sort Fazzari, Pietro
title Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling
title_short Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling
title_full Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling
title_fullStr Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling
title_full_unstemmed Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling
title_sort cell autonomous regulation of hippocampal circuitry via aph1b-γ-secretase/neuregulin 1 signalling
description Neuregulin 1 (NRG1) and the γ-secretase subunit APH1B have been previously implicated as genetic risk factors for schizophrenia and schizophrenia relevant deficits have been observed in rodent models with loss of function mutations in either gene. Here we show that the Aph1b-γ-secretase is selectively involved in Nrg1 intracellular signalling. We found that Aph1b-deficient mice display a decrease in excitatory synaptic markers. Electrophysiological recordings show that Aph1b is required for excitatory synaptic transmission and plasticity. Furthermore, gain and loss of function and genetic rescue experiments indicate that Nrg1 intracellular signalling promotes dendritic spine formation downstream of Aph1b-γ-secretase in vitro and in vivo. In conclusion, our study sheds light on the physiological role of Aph1b-γ-secretase in brain and provides a new mechanistic perspective on the relevance of NRG1 processing in schizophrenia.
publisher eLife Sciences Publications, Ltd
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073283/
_version_ 1612107096298356736

Similar Items