Kinesin participates in melanosomal movement along melanocyte dendrites

Movement of melanosomes along melanocyte dendrites is necessary for the tra nsfer of melanin pigment from melanocytes to basal and suprabasal keratinoc ytes, an event critical to epidermal photoprotection and maintenance of nor mal skin color. Recent murine data suggest that in melanocyte dendrites the microtubule-associated melanosome movement is bidirectional and that actin -associated myosin V secures the peripheral melanosomes, preparing them to be transferred to surrounding keratinocytes. We now report that human melan ocytes express high levels of kinesin, a molecule that participates in micr otubule-associated transport of organelles in other cell types, and that ul trastructurally kinesin molecules are closely associated with melanosomes. To determine whether kinesin participates in melanosomal transport, culture d melanocytes were treated with sense or antisense oligonucleotides complem entary to kinesin heavy chain sequences. Antisense oligonucleotides decreas ed kinesin protein levels and inhibited the bidirectional movement of the m elanosomes, promoting their backward movement. Furthermore, guinea pigs wer e exposed to ultraviolet B irradiation, known to enhance transport of melan osomes from melanocytes to epidermal keratinocytes, and then were treated w ith kinesin sense or antisense oligonucleotides. The areas that were treate d with kinesin antisense oligonucleotides showed significantly less pigment ation clinically and histologically than control (sense) oligonucleotide-tr eated areas. As observed ultrastructurally, in antisense-treated areas mela nosomes remained in melanocyte dendrites but over several days were not tra nsferred to the surrounding keratinocytes. Our study supports a major role for kinesin in microtubule-associated anterograde melanosomal transport in human melanocyte dendrites.