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The amyloid precursor protein forms plasmalemmal clusters via its pathogenic amyloid-? domain.

ABSTRACT: The amyloid precursor protein (APP) is a large, ubiquitous integral membrane protein with a small amyloid-? (A?) domain. In the human brain, endosomal processing of APP produces neurotoxic A?-peptides, which are involved in Alzheimer's disease. Here, we show that the A? sequence exerts a physiological function when still present in the unprocessed APP molecule. From the extracellular site, A? concentrates APP molecules into plasmalemmal membrane protein clusters. Moreover, A? stabilization of clusters is a prerequisite for their targeting to endocytic clathrin structures. Therefore, we conclude that the A? domain directly mediates a central step in APP trafficking, driving its own conversion into neurotoxic peptides.

SUBMITTER: Schreiber A

PROVIDER: S-EPMC3309305 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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The amyloid precursor protein forms plasmalemmal clusters via its pathogenic amyloid-β domain.

Schreiber Arne A Fischer Sebastian S Lang Thorsten T

Biophysical journal 20120320 6

The amyloid precursor protein (APP) is a large, ubiquitous integral membrane protein with a small amyloid-β (Aβ) domain. In the human brain, endosomal processing of APP produces neurotoxic Aβ-peptides, which are involved in Alzheimer's disease. Here, we show that the Aβ sequence exerts a physiological function when still present in the unprocessed APP molecule. From the extracellular site, Aβ concentrates APP molecules into plasmalemmal membrane protein clusters. Moreover, Aβ stabilization of cl ...[more]

PMID: 22455924

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