Alzheimer's disease amyloid precursor protein on the surface of cortical neurons in primary culture co-localizes with adhesion patch components.
Immunofluorescence on primary dissociated rat neuronal cultures (cortical, hippocampal, and cerebellar) and organotypic hippocampal cultures was used to investigate the pattern of distribution of cell-surface amyloid protein (APP). Antibodies directed against the extracellular (N-terminal) portion of APP or against the entire molecule, but not against the C-terminal portion, revealed a striking segmental pattern of immunoreactivity along both axons and dendrites of all neuronal types tested. The pattern first developed between 24 and 48 h in culture. The segments showed co-localization with beta 1-integrin and talin immunoreactivities, but not with GAP-43 or clathrin, indicating that they may mark adhesion patches. Confocal laser microscopy supported a surface location for the APP responsible for the segmented pattern on neurites, as did the reduction of segmental immunoreactivity after exposure to mu-calpain or trypsin. It is conjectured that APP may have a role in cell-substratum interactions in the medium term, during such events as synaptic plasticity and neurite stability during extension.
Storey
E
E
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia. e.storey@pathology.unimelb.edu.au
Beyreuther
K
K
Masters
C L
CL
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016608:Talin / Q000378:metabolism; D014018:Tissue Distribution
D016564:Amyloid beta-Protein Precursor; D019012:Integrin beta1; D016608:Talin