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Agouti protein, mahogunin, and attractin in pheomelanogenesis and melanoblast‐like alteration of melanocytes: a cAMP‐independent pathway
Author(s) -
Hida Tokimasa,
Wakamatsu Kazumasa,
Sviderskaya Elena V.,
Donkin Andrew J.,
Montoliu Lluis,
Lynn Lamoreux M.,
Yu Bin,
Millhauser Glenn L.,
Ito Shosuke,
Barsh Gregory S.,
Jimbow Kowichi,
Bennett Dorothy C.
Publication year - 2009
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2009.00582.x
Subject(s) - melanocortin 1 receptor , melanocyte , melanocortin , microphthalmia associated transcription factor , signal transduction , melanin , cancer research , hypopigmentation , waardenburg syndrome , chemistry , hormone , microbiology and biotechnology , tyrosinase , endocrinology , biology , enzyme , biochemistry , phenotype , melanoma , genetics , gene
Summary Melanocortin‐1 receptor (MC1R) and its ligands, α‐melanocyte stimulating hormone (αMSH) and agouti signaling protein (ASIP), regulate switching between eumelanin and pheomelanin synthesis in melanocytes. Here we investigated biological effects and signaling pathways of ASIP. Melan‐a non agouti ( a/a ) mouse melanocytes produce mainly eumelanin, but ASIP combined with phenylthiourea and extra cysteine could induce over 200‐fold increases in the pheomelanin to eumelanin ratio, and a tan‐yellow color in pelletted cells. Moreover, ASIP‐treated cells showed reduced proliferation and a melanoblast‐like appearance, seen also in melanocyte lines from yellow ( A y /a and Mc1r e / Mc1r e ) mice. However ASIP‐YY, a C‐terminal fragment of ASIP, induced neither biological nor pigmentary changes. As, like ASIP, ASIP‐YY inhibited the cAMP rise induced by αMSH analog NDP‐MSH, and reduced cAMP level without added MSH, the morphological changes and depigmentation seemed independent of cAMP signaling. Melanocytes genetically null for ASIP mediators attractin or mahogunin ( Atrn mg‐3J/mg‐3J or Mgrn1 md‐nc/md‐nc ) also responded to both ASIP and ASIP‐YY in cAMP level, while only ASIP altered their proliferation and (in part) shape. Thus, ASIP–MC1R signaling includes a cAMP‐independent pathway through attractin and mahogunin, while the known cAMP‐dependent component requires neither attractin nor mahogunin.