The secretory beta-amyloid precursor protein is a motogen for human epidermal keratinocytes.
Cell migration is known to be triggered by constituents of the extracellular matrix such as fibronectin and by soluble mediators commonly summarized as motogens. Many growth factors such as the epidermal growth factor (EGF) have been shown to act as motogens. Recently, the secretory N-terminal portion of the beta-amyloid precursor protein (sAPP) has been identified as a keratinocyte growth factor. Hence, in this study we analysed whether sAPP stimulates also keratinocyte migration employing the stroboscopic cell motility assay. The migration velocity as well as the frequency of lamellipodia protrusion and ruffle formation were increased about two-fold thus corresponding to the effect of EGF. Using a newly developed beta1-integrin migration track assay we observed that sAPP increased the proportion of migrating keratinocytes and their directional persistence. sAPP appeared to operate synergistically with fibronectin with respect to its motogenic effect. Using a modified Boyden chamber assay we showed that sAPP besides its chemokinetic effect functions as a chemoattractant. Like EGF, sAPP exerted its motogenic effect through the activation of Rac kinase but the receptor for sAPP appears to be distinct. The results suggest that sAPP operates as a motogen in the human epidermis, where it may participate in the regulation of reepithelialization during wound healing.
Kirfel
Gregor
G
Institute for Cell Biology and Bonner Forum Biomedizin, University of Bonn, Bonn, Germany. g.kirfel@uni-bonn.de
Borm
Bodo
B
Rigort
Alexander
A
Herzog
Volker
V
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D020033:Protein Isoforms / Q000378:metabolism / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D006133:Growth Substances; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt