In:
Neurodegenerative Diseases, S. Karger AG, Vol. 13, No. 2-3 ( 2014), p. 72-74
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Generation of amyloid-β peptide is at the beginning of a cascade that leads to Alzheimer's disease. Amyloid precursor protein (APP) as well as β- and & #947;-secretases are the principal players involved in amyloid-β (Aβ) production, while α-secretase cleavage on APP prevents Aβ deposition. A disintegrin and metalloproteinase 10 (ADAM10) has been demonstrated to act as α-secretase in neurons. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 Although localization of ADAM10 in the synaptic membrane is the key for its shedding activity, currently, very little is known about the mechanisms that control the synaptic abundance of ADAM10. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Two established forms of long-term activity-dependent plasticity, i.e. long-term potentiation and long-term depression (LTD), differentially regulate the synaptic availability and activity of ADAM10. Long-term potentiation decreases ADAM10 surface levels and activity by promoting its endocytosis. This process is mediated by activity-regulated association of ADAM10 with the clathrin adaptor protein 2 (AP2) complex. Conversely, LTD fosters ADAM10 insertion in the membrane and stimulates its activity. Furthermore, ADAM10 interaction with synapse-associated protein 97 (SAP97) is necessary for LTD-induced ADAM10 trafficking and required for LTD maintenance and LTD-induced spine morphology changes. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Regulated interaction of ADAM10 with SAP97 and AP2 discloses a novel physiological mechanism of ADAM10 activity regulation at the synapses. This phenomenon produces a situation whereby synaptically regulated ADAM10 activity is positioned to modulate synaptic functioning.
Type of Medium:
Online Resource
ISSN:
1660-2854
,
1660-2862
Language:
English
Publisher:
S. Karger AG
Publication Date:
2014
detail.hit.zdb_id:
2126858-7
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