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2009 | 69 | 3 |
Tytuł artykułu

Dissasembly of shank and homer synaptic clusters is driven by soluble betta-amyloid through divergent NMDAR-dependent signalling pathways

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Disruption of the postsynaptic density (PSD) is thought to be responsible for synaptic dysfunction and loss in early-stage Alzheimer’s disease. We show that Aβ disrupts two other scaffold proteins, Homer1b and Shank1. Treatment of cortical neurons with soluble Ab results in rapid thinning of the PSD, decreased synaptic levels of Homer1b and Shank1, and reduced synaptic mGluR1 levels; the latter changes require NMDAR and voltage-dependent calcium channel (VDCC) activity. We also show that de novo protein synthesis is required for the declustering effects of Aβ on Homer1b (but not Shank1) and that, in contrast to PSD-95, Aβ-induced Homer1b and Shank1cluster disassembly does not depend on proteasome activity. The regulation of Homer1b and Shank1 by Aβ diverges in two other respects: (1) whereas the activity of both NMDAR and VDCC is required for Aβ-induced declustering of Homer1b, Aβinduced declustering of Shank1 only requires NMDAR activity; (2) whereas the effects of Aβ on Homer1b involve engagement of the PI-3K pathway and PP2B activity, those on Shank1 involve activation of ERK/RSK. Thus, Aβ recruits discrete signaling pathways to rapidly reduce the synaptic localization of major components of the PSD and to regulate the availability of mGluR1.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
69
Numer
3
Opis fizyczny
p.340
Twórcy
autor
  • Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
autor
  • Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
autor
  • Department of Neurological and Psychiatric Sciences, university of Bari, Bari, Italy
autor
  • Department of Neurological and Psychiatric Sciences, university of Bari, Bari, Italy
autor
  • Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-c93b7455-c6a2-44d4-a39c-0f75c24e95f2
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