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Agouti protein, mahogunin, and attractin in pheomelanogenesis and melanoblast-like alteration of melanocytes: a cAMP-independent pathway
- Source :
- Pigment Cell & Melanoma Research, Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2009
- Publisher :
- John Wiley & Sons, 2009.
-
Abstract
- Melanocortin-1 receptor (MC1R) and its ligands, a-melanocyte stimulating hormone (aMSH) 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.<br />Moreover, ASIP-treated cells showed reduced proliferation and a melanoblast-like appearance, seen also in melanocyte lines from yellow (Ay ⁄ a and Mc1re ⁄ Mc1re) 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 aMSH 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 (Atrnmg-3J ⁄ mg-3J or Mgrn1md-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.<br />Parts of the research were supported by Wellcome Trust program grants 064583 and 078327 to D.C.B. and E.V.S.; the Japan Society for the Promotion of Science KAKENHI (grants 20790808 to T.H. and 18591262 and 20591357 to K.W. and S.I.); a Grant-in-Aid from the Japanese Ministry of Health, Labour and Welfare (K.J.), the Spanish Ministry of Education and Science BFU2006-12185 (L.M.), the South West Academic Network (A.J.D. and E.V.S.), and NIH grant DK064265 (B.Y. and G.L.M.).
- Subjects :
- Agouti
Agouti Protein
Mice
0302 clinical medicine
Depigmentation
Mc1r
Cyclic AMP
Receptor
Pheomelanin
Cells, Cultured
Mice, Knockout
0303 health sciences
integumentary system
Pigmentation
digestive, oral, and skin physiology
3. Good health
Cell biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Agouti Signaling Protein
Melanocytes
Melanoblast
medicine.symptom
Signal transduction
Receptor, Melanocortin, Type 1
Signal Transduction
medicine.medical_specialty
Ubiquitin-Protein Ligases
Dermatology
Biology
Melanocyte
General Biochemistry, Genetics and Molecular Biology
Mahogunin
03 medical and health sciences
cAMP
Internal medicine
medicine
Animals
Hair Color
Cell Shape
Cell Proliferation
030304 developmental biology
Melanins
Attractin
Membrane Proteins
Original Articles
Mice, Inbred C57BL
Endocrinology
Cysteine
Hormone
Subjects
Details
- Language :
- English
- ISSN :
- 17551471
- Database :
- OpenAIRE
- Journal :
- Pigment Cell & Melanoma Research, Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....873e28e8c7399a5be2ddc595055f7da9