sAPP as a regulator of dendrite motility and melanin release in epidermal melanocytes and melanoma cells

Abstract

Numerous factors including ultraviolet (UV) radiation and growth factors regulate the specific function of epidermal melanocytes. A recently discovered epidermal growth factor is sAPP, the soluble N-terminal ectodomain of the beta-amyloid precursor protein (APP). Using whole mount preparations of isolated human epidermis, we detected a small population of basal cells, which expressed exceptionally high levels of APP. These cells were identified as melanocytes, which, similar to keratinocytes and neuronal cells, expressed the three APP isoforms 695, 751, and 770. They differed in their expression pattern from that of neuronal cells by expressing only low levels of APP 695. Melanocytes and melanoma cells in vitro released, in addition to keratinocytes, large quantities of sAPP. Because of its growth factor function, we studied possible effects of sAPP on melanocytes. Recombinant sAPP strongly increased lamellipodia activity at dendritic tips, an effect that coincided with increased release of melanin particles. Our observations point to the possible use of APP as an immunocytochemical marker for melanocytes. They suggest that sAPP derived from keratinocytes and/or melanocytes belongs to a family of factors operating in the paracrine and/or autocrine regulation of melanocyte function.

Membrane ruffles in cell migration: indicators of inefficient lamellipodia adhesion and compartments of actin filament reorganization

“…To validate the assumed relationship between lamellipodia adhesion and ruffle formation, we applied the highresolution SACED cell motility assay [20,22,23] that allows to acquire and quantify various parameters of cell migration and motility simultaneously, and has been successfully used to characterize the motogenic activity of growth factors on epidermal keratinocytes and melanocytes [22,31]. To learn more about the signals and mechanisms involved in ruffle formation, we investigated the structural organization and the protein composition of membrane ruffles, and analyzed Fig.…”

Solution Conformation and Heparin-induced Dimerization of the Full-length Extracellular Domain of the Human Amyloid Precursor Protein

“…sAPPa is an important growth factor in the development of the human brain and in adult neurogenesis, 12,18 paralleling its importance in other human tissues. 19,42 While the molecular mechanisms of its actions in postmitotic neurons remain unclear, sAPPa has been shown to exert a memoryenhancing effect. 43 Moreover, neural activity can lead to a higher secretion of sAPPa 44 and sAPPa has been shown to be neuroprotective against different types of insults.…”

“…16 In vivo experiments have led to the hypothesis that AD may be caused in part by a lack of sAPPa, in addition to the toxic effects of Ab. 45 While it has been shown that sAPPa acts as an autocrine or paracrine growth or differentiation factor 18,19,42 and that it binds to defined patches on the cell surface, 46 no specific receptor for sAPPa has been identified so far. The availability of structural models of sAPPa may, therefore, provide tools for investigating the binding partners and mechanisms of action of this important APP fragment.…”

Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract

“…Increased expression of amyloid protein family members can influence cancer development in several different tumour types (Nakagawa et al 1999, Meng et al 2001, Hansel et al 2003, Quast et al 2003, Baldus et al 2004, Ko et al 2004, Mauri et al 2005, Li et al 2006. Neuroblastoma, a malignant tumour of neural crest origin, is the only tumour type that has been reported to express high levels of APLP1 (Wasco et al 1992).…”