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PMID: 1281980 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion.

The Biochemical journal ·Vol. 288 ( Pt 3) ·1992-12-15 ·Pages 1053-9

Ghiso J, Rostagno A, Gardella JE, Liem L, Gorevic PD, Frangione B

Abstract

Amyloid beta (A beta), the major constituent of the fibrils composing senile plaques and vascular amyloid deposits in Alzheimer's disease (AD) and related disorders, is a 39-42-residue self-aggregating degradation peptide of a larger multidomain membrane glycoprotein designated amyloid precursor protein (APP). An array of biological functions has been assigned to different APP domains, including growth regulation, neurotoxicity, inhibitory activity of serine proteinases and promotion of cell-cell and cell-matrix interactions. A beta is generated through an as-yet-unknown catabolic pathway that by-passes or inhibits the cleavage of APP within the A beta sequence. We have identified a 16 kDa intermediate APP C-terminal fragment containing A beta in leptomeningeal vessels of aged normal individuals and AD patients by means of its immunoreactivity with a panel of four different anti-(APP C-terminal) antibodies, indicating a different pathway of APP processing. Previous studies have indicated that the APP C-terminal domain is the most likely to be involved in cell-matrix interactions. A 109-amino-acid construct C109 with a sequence analogous to the C-terminal of APP (positions 587-695 of APP695), similar in length and immunoreactivity to the 16 kDa fragment, was found to promote cell adhesion. By use of synthetic peptides, this activity was initially located to the extracellular 28 residues of A beta. Inhibition studies demonstrated that the sequence RHDS (amino acids 5-8 of A beta, corresponding to residues 601-604 of APP695 was responsible for the adhesion-promoting activity. The interaction is dependent on bivalent cations and can be blocked either by the tetrapeptides RHDS and RGDS or by an anti-(beta 1 integrin) antibody. Thus, through integrin-like surface receptors, APP or its derivative proteolytic fragments containing the sequence RHDS may modulate cell-cell or cell-matrix interactions.

MeSH Terms
Aged Aged, 80 and over Alzheimer Disease/immunology,pathology Amino Acid Sequence Amyloid beta-Peptides/analysis,immunology,metabolism Amyloid beta-Protein Precursor/analysis,immunology,metabolism Animals Antibodies Base Sequence Brain Chemistry Cell Adhesion/physiology Cell Communication/physiology Cells, Cultured Epitopes/analysis Humans Immunoblotting Meninges/chemistry Middle Aged Molecular Sequence Data Peptide Fragments/analysis,immunology,metabolism Protein Processing, Post-Translational Rabbits
Chemicals
Amyloid beta-Peptides Amyloid beta-Protein Precursor Antibodies Epitopes Peptide Fragments
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ghiso J
Department of Pathology, New York University Medical Center, NY 10016.
Rostagno A
Gardella J E
Liem L
Gorevic P D
Frangione B
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2881053
Published
1992-12-15
Pages
1053-9
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1131993
Subset
IM
Grants
NIA NIH HHS · AG 05891 · United States
NIA NIH HHS · AG 08721 · United States
NIA NIH HHS · AG 10491 · United States
External Links
PubMed source DOI: 10.1042/bj2881053 PMC Full Text View journal details
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