title: Melanin transfer in human skin cells is mediated by filopodia--a model for homotypic and heterotypic lysosome-related organelle transfer.
abstract: Transfer of the melanocyte-specific and lysosome-related organelle, the melanosome, from melanocytes to keratinocytes is crucial for the protection of the skin against harmful ultraviolet radiation (UVR)--our main physiological cutaneous stressor. However, this commonplace event remains a most enigmatic process despite several early hypotheses. Recently, we and others have proposed a role for filopodia in melanin transfer, although conclusive experimental proof remained elusive. Using known filopodial markers (MyoX/Cdc42) and the filopodial disrupter, low-dose cytochalasin-B, we demonstrate here a requirement for filopodia in melanosome transfer from melanocytes to keratinocytes and also, unexpectedly, between keratinocytes. Melanin distribution throughout the skin represents the key phenotypic event in skin pigmentation. Melanocyte filopodia were also necessary for UVR-stimulated melanosome transfer, as this was also inhibited by MyoX knockdown and low-dose cytochalasin-B. Knockdown of keratinocyte MyoX protein, in its capacity as a phagocytosis effector, resulted in the inhibition of melanin uptake by keratinocytes. This indicates a central role for phagocytosis by keratinocytes of melanocyte filopodia. In summary, we propose a new model for the regulation of pigmentation in human skin cells under both constitutive and facultative (post-UVR) conditions, which we call the "filopodial-phagocytosis model." This model also provides a unique and highly accessible way to study lysosome-related organelle movement between mammalian cells.
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Suman K
authors.initials: SK
authors.lastname: Singh
authors.forename: Robin
authors.initials: R
authors.lastname: Kurfurst
authors.forename: Carine
authors.initials: C
authors.lastname: Nizard
authors.forename: Sylvianne
authors.initials: S
authors.lastname: Schnebert
authors.forename: Eric
authors.initials: E
authors.lastname: Perrier
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D001692:Biological Transport; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011554:Pseudopodia / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D017931:DNA Primers; D008543:Melanins