APP and adhesion of axonal growth cones

SOSA, L., SIMON, G.C., ESTRADA-BERNAL, A., POSTMA, N., PFENNINGER, K.H.

San Diego

Congreso; 40th Annual Meeting Society for Neuroscience; 2010

Society of Neuroscience

Amyloid precursor protein (APP) is a large integral membrane glycoprotein that has been implicated in the pathogenesis of Alzheimer disease. Recent studies have suggested that APP interacts with integrin, and that both proteins may be involved in neuronal migration during brain development (Young-Pearse et al, 2008). APP has been detected in nerve growth cones (Sabo et al, 2003), but its function remains unclear. Here we report on the enrichment and possible functions of APP in the axonal growth cone in mouse brain. APP not only is present but is highly enriched relative to homogenate in growth cones isolated from fetal and newborn mouse brain and, therefore, is likely to play a functionally important role. By co-immunoprecipitation APP and alfa 3 beta 1 integrin (Itga3b1) can be shown to interact in growth cones, and immunofluorescence reveals extensive co-localization. APP gain and loss of function experiments, using neurons after transfection (with APP-encoding plasmids or APP-targeted siRNA) or from mutant mice (the Down syndrome model mouse Ts65Dn, which has three copies of the APP gene, or APP-/- mice), were used to begin to address the question of APP function. Ts65Dn mice over-express APP in their growth cones by about 50%, as expected from gene dosage. On a laminin matrix in culture these growth cones are larger (+55±9%), have an increased adhesive area as seen by interference reflection microscopy (+69±15%) and form a greater number of filopodia (+50±10%), as compared with euploid litter mates (p