Melanin transfer in human skin cells is mediated by filopodia—a model for homotypic and heterotypic lysosome‐related organelle transfer

Abstract

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Bone morphogenetic proteins differentially regulate pigmentation in human skin cells

“…We have not evaluated the role of p38MAPK and PI3-K in the filopodia formation in human MC; however, these pathways were found to be involved in the regulation of filopodia formation in other cell lines (Gadea et al, 2004;Vadlamudi et al, 1999;Adam et al, 1998). The involvement of PI3-K in BMP6-induced melanin transfer substantiates our recently proposed view of how MC filopodia interact with KC phagocytosis during the melanin transfer process (Singh et al, 2010). Here the motor protein MYOX, a recognised effector of phagocytosis, acts as a molecular link between PI3-K activation and pseudopodia extension during phagocytosis (Cox et al, 2002).…”

“…2A-C). Further confirmation that these MC were UVBresponsive was provided by the expected upregulation of MITF and tyrosinase (TYR) and melanin transfer-associated markers CDC42 and MYOX (Scott et al, 2002;Singh et al, 2010) ( Fig. 2A,B) after irradiation.…”

“…UVR also stimulates MC dendricity, filopodia formation and melanin transfer (Scott et al, 2002;Singh et al, 2010). However, a significant gap remains in our understanding of just how melanin transfer is controlled at steady state conditions in skin.…”

“…MYOX is thought to act downstream of the GTPase family member CDC42, a master regulator of filopodia formation and melanin transfer (Scott et al, 2002;Singh et al, 2010). Here we show that BMP6 upregulates the expression of several filopodiaassociated proteins FSCN1, VASP, ITGB1 and ITGB3 in MC, while BMP4, inhibited this.…”

“…Several hypotheses have been proposed including: (i) cytophagocytosis of MC dendrite tips (Seiberg et al, 2000), (ii) exocytosis of melanosomes and subsequent uptake via phagocytosis into KC (Marks and Seabra, 2001;Virador et al, 2002) and (iii) filopodia-mediated melanosome transfer (Singh et al, 2010;Singh et al, 2008;Beaumont et al, 2011;Zhang et al, 2004;Scott et al, 2002). The role of filopodia in the transfer of melanosomes to keratinocytes was originally proposed by Scott and colleagues (Scott et al, 2002), and we extended this further in our recent report that proposed a 'filopodial-phagocytosis model' for melanin transfer (Singh et al, 2010). However, the underlying regulatory and signalling pathways involved remain poorly defined, and this is the subject of the current study.…”