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Expression and signaling of the tyrosine kinase FGFR2b/KGFR regulates phagocytosis and melanosome uptake in human keratinocytes
Author(s) -
Belleudi Francesca,
Purpura Valeria,
Scrofani Cristina,
Persechino Flavia,
Leone Laura,
Torrisi Maria Rosaria
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-162156
Subject(s) - phagocytosis , melanosome , microbiology and biotechnology , tyrosine kinase , receptor tyrosine kinase , kinase , biology , signal transduction , cancer research , melanin , biochemistry
Membrane and actin cytoskeleton dynamics during phagocytosis can be triggered and amplified by the signal transduction of receptor tyrosine kinases. The epidermal keratinocytes appear to use the phagocytic mechanism of uptake to ingest melano‐somes released by the melanocytes and play a pivotal role in the transfer process. We have previously demonstrated that the keratinocyte growth factor KGF/ FGF7 promotes the melanosome uptake through activation of its receptor tyrosine kinase FGFR2b/KGFR. The aim of the present study was to investigate the contribution of KGFR expression, activation, and signaling in regulating the phagocytic process and the melanosome transfer. Phagocytosis was analyzed in vitro using fluorescent latex beads on human keratin‐ocytes induced to differentiate. Melanosome transfer was investigated in keratinocyte‐melanocyte cocul‐tures. KGFR depletion by small interfering RNA microinjection and overexpression by transfection of wild type or defective mutant KGFR were performed to demonstrate the direct effect of the receptor on phagocytosis and melanosome transfer. Colocalization of the phagocytosed beads with the internalized receptors in phagolysosomes was analyzed by optical sectioning and 3‐dimensional reconstruction. KGFR ligands triggered phagocytosis and melanosome transfer in differentiated keratinocytes, and receptor kinase activity and signaling were required for these effects, suggesting that FGFR2b/KGFR expression/activity and PLCγ signaling pathway play crucial roles in phagocytosis.—Belleudi, F., Purpura, V., Scrofani, C., Persechino, F., Leone, L., and Torrisi, M. R. Expression and signaling of the tyrosine kinase FGFR2b/KGFR regulates phagocytosis and melano‐some uptake in human keratinocytes. FASEB J. 25, 170–181 (2011). www.fasebj.org