Interaction of beta-amyloid peptides with integrins in a human nerve cell line.
beta-Amyloid accumulates as extracellular aggregates in Alzheimer's-afflicted brain tissue, but it also is secreted by healthy tissue, for reasons not yet established. One possibility is that beta-amyloid, which contains a sequence (RHDS) homologous to the cell-binding domain of fibronectin, may modulate integrin function, a possibility supported by previous data from non-neuronal cells (Ghiso et al., Biochem. J., 288 (1992) 1053-1059). The current work shows that functional interaction with beta-amyloid peptides is also supported by integrins in neuronal cells. Experiments used the SH-SY5Y human neuroblastoma cell line, which was shown to contain integrins that mediated cell adhesion to substratum-bound fibronectin. Adhesion to fibronectin was partially blocked by synthetic beta-amyloid peptides containing the RHDS sequence. beta-Amyloid sequences adsorbed to substratum themselves were found to mediate cell adhesion, although less effectively than fibronectin. Anti-integrin blocked the peptide-mediated adhesion, at doses commensurate with those blocking fibronectin-mediated adhesion. The data support the hypothesis that beta-amyloid peptides could physiologically, and perhaps pathogenically, modulate the activity of neuronal integrins, important cell surface receptors known to control protein kinase activities, Ca2+ levels, gene expression and organization of the cytoskeleton.
Sabo
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Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
Lambert
M P
MP
Kessey
K
K
Wade
W
W
Krafft
G
G
Klein
W L
WL
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000906:Antibodies; D002448:Cell Adhesion; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000097:blood; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D000906:Antibodies; D005353:Fibronectins; D016023:Integrins; D010455:Peptides