Expression and signaling of the tyrosine kinase FGFR2b/KGFR regulates phagocytosis and melanosome uptake in human keratinocytes
Expression and signaling of the tyrosine kinase FGFR2b/KGFR regulates phagocytosis and melanosome uptake in human keratinocytes
复制标题
DOI：
10.1096/fj.10-162156
复制
发表时间：
2011-01-01
期刊：
影响因子：
4.8
通讯作者：
Torrisi, Maria Rosaria
中科院分区：
文献类型：
--
作者：
Belleudi, Francesca;Purpura, Valeria;Torrisi, Maria Rosaria
吞噬过程中的膜和肌动蛋白细胞骨架动力学可以通过受体酪氨酸激酶的信号转导来触发和放大。表皮角质形成细胞似乎利用吞噬细胞的摄取机制来摄取黑素细胞释放的黑素体，并在转移过程中发挥关键作用。我们之前已经证明角质形成细胞生长因子 KGF/FGF7 通过激活其受体酪氨酸激酶 FGFR2b/KGFR 来促进黑素体的摄取。本研究的目的是研究 KGFR 表达、激活和信号传导在调节吞噬过程和黑素体转移中的贡献。使用荧光乳胶珠对诱导分化的人角质形成细胞进行体外吞噬作用分析。在角质形成细胞-黑素细胞共培养物中研究了黑素体转移。通过小干扰RNA显微注射来消除KGFR，并通过转染野生型或缺陷突变型KGFR来过度表达，以证明受体对吞噬作用和黑素体转移的直接影响。通过光学切片和 3 维重建来分析吞噬珠与吞噬溶酶体中内化受体的共定位。 KGFR 配体触发分化角质形成细胞中的吞噬作用和黑素体转移，这些作用需要受体激酶活性和信号传导，这表明 FGFR2b/KGFR 表达/活性和 PLC γ 信号通路在吞噬作用中发挥着至关重要的作用。-Belleudi, F., Purpura, V., Scrofani, C., Persechino, F., Leone, L., 和 Torrisi, M. R. 的表达和信号传导酪氨酸激酶 FGFR2b/KGFR 调节人角质形成细胞的吞噬作用和黑素体摄取。 FASEB J. 25, 170-181 (2011)。 www.fasebj.org
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 melanosomes 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 keratinocytes induced to differentiate. Melanosome transfer was investigated in keratinocyte-melanocyte cocultures. 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 PLC gamma 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 melanosome uptake in human keratinocytes. FASEB J. 25, 170-181 (2011). www.fasebj.org