Agouti protein, mahogunin, and attractin in pheomelanogenesis and melanoblast-like alteration of melanocytes: a cAMP-independent pathway.
Agouti protein, mahogunin, and attractin in pheomelanogenesis and melanoblast-like alteration of melanocytes: a cAMP-independent pathway.
复制标题
DOI：
10.1111/j.1755-148x.2009.00582.x
复制
发表时间：
2009-10
影响因子：
4.3
通讯作者：
Bennett DC
中科院分区：
文献类型：
--
作者：
Hida T;Wakamatsu K;Sviderskaya EV;Donkin AJ;Montoliu L;Lynn Lamoreux M;Yu B;Millhauser GL;Ito S;Barsh GS;Jimbow K;Bennett DC
黑素皮质素-1受体（MC 1 R）及其配体α-黑素细胞刺激素（α-melanocyte stimulating hormone，αMSH）和凝集素信号蛋白（agglutinalsignaling protein，ASIP）调节黑素细胞中真黑素和褐黑素合成之间的转换。本文研究了ASIP的生物学效应和信号通路。Melan-a non agglutination（a/a）小鼠黑素细胞主要产生真黑素，但ASIP与苯基硫脲和额外的半胱氨酸组合可诱导褐黑素与真黑素的比率增加200倍以上，并且在沉淀的细胞中呈现棕黄色。此外，ASIP处理的细胞表现出减少的增殖和成黑色素细胞样的外观，也见于黄色（Ay/a和Mc 1 re/Mc 1 re）小鼠的黑素细胞系。然而，ASIP的C末端片段ASIP-YY既不诱导生物学变化也不诱导色素变化。ASIP-YY与ASIP一样，抑制了αMSH类似物NDP-MSH诱导的cAMP升高，在不加MSH的情况下，ASIP-YY也能降低cAMP水平，因此，细胞形态学改变和色素脱失似乎与cAMP信号无关。黑素细胞遗传上对ASIP介质吸引素或Mahogunin（Atrnmg-3 J/mg-3 J或Mgrn 1 md-nc/md-nc）无效，也在cAMP水平上对ASIP和ASIP-YY两者作出反应，而仅ASIP改变它们的增殖和（部分）形状。因此，ASIP-MC 1 R信号传导包括通过吸引素和mahogunin的cAMP非依赖性途径，而已知的cAMP依赖性组分既不需要吸引素也不需要mahogunin。
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 (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 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 (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.