Centaureidin promotes dendrite retraction of melanocytes by activating Rho.
Melanosomes synthesized within melanocytes are transferred to keratinocytes through dendrites, resulting in a constant supply of melanin to the epidermis, and this process determines skin pigmentation. During screening for inhibitors of melanosome transfer, we found a novel reagent, centaureidin, that induces significant morphological changes in normal human epidermal melanocytes and inhibits melanocyte dendrite elongation, resulting in a reduction of melanosome transfer in an in vitro melanocyte-keratinocyte co-culture system. Since members of the Rho family of small GTP-binding proteins act as master regulators of dendrite formation, and activated Rho promotes dendrite retraction, we studied the effects of centaureidin on the small GTPases. In in vitro binding assay, centaureidin activated Rho and furthermore, a Rho inhibitor (C. botulinum C3 exoenzyme), a Rho kinase inhibitor (Y27632) and a small GTPase inhibitor (Toxin B) blocked dendrite retraction induced by centaureidin. These results suggest centaureidin could act via the Rho signaling pathway, and it may directly or indirectly activate Rho. Thus, centaureidin appears to inhibit dendrite outgrowth from melanocytes by activating Rho, resulting in the inhibition of melanosome transfer from melanocytes to keratinocytes.
Ito
Yuko
Y
POLA Laboratories, POLA Chemical Industries, Inc., 560 Kashio-cho, Totsuka-ku, Yokohama 244-0812, Japan. y-itou@pola.co.jp
Kanamaru
Akiko
A
Tada
Akihiro
A
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D001905:Botulinum Toxins / Q000494:pharmacology; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020460:Melanosomes / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D000577:Amides; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005419:Flavonoids; D008543:Melanins; D011725:Pyridines; C031815:toxB protein, Clostridium difficile; C108830:Y 27632; C083161:centaureidin; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins