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

• Autorzy: Roselli F. , Wegerich Y. , Defazio G. , Livrea P. , Almeida O.
• 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.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.340

Twórcy

autor

Roselli F.

• Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany

autor

Wegerich Y.

• Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany

autor

Defazio G.

• Department of Neurological and Psychiatric Sciences, university of Bari, Bari, Italy

autor

Livrea P.

• Department of Neurological and Psychiatric Sciences, university of Bari, Bari, Italy

autor

Almeida O.

• Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany