Premium
Essential role of the molecular chaperone gp96 in regulating melanogenesis
Author(s) -
Zhang Yongliang,
Helke Kristi L.,
Coelho Sergio G.,
Valencia Julio C.,
Hearing Vincent J.,
Sun Shaoli,
Liu Bei,
Li Zihai
Publication year - 2014
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/pcmr.12165
Subject(s) - melanosome , melanocyte , tyrosinase , microbiology and biotechnology , gene knockdown , endoplasmic reticulum , melanin , chaperone (clinical) , biology , downregulation and upregulation , wnt signaling pathway , heat shock protein , signal transduction , biochemistry , gene , genetics , enzyme , medicine , melanoma , pathology
Summary Through a process known as melanogenesis, melanocyte produces melanin in specialized organelles termed melanosomes, which regulates pigmentation of the skin, eyes, and hair. G p96 is a constitutively expressed heat shock protein in the endoplasmic reticulum whose expression is further upregulated upon ultraviolet irradiation. However, the roles and mechanisms of this chaperone in pigmentation biology are unknown. In this study, we found that knockdown of gp96 by RNA interference significantly perturbed melanin synthesis and blocked late melanosome maturation. G p96 knockdown did not impair the expression of tyrosinase, an essential enzyme in melanin synthesis, but compromised its catalytic activity and melanosome translocation. Further, mice with melanocyte‐specific deletion of gp96 displayed decreased pigmentation. A mechanistic study revealed that the defect in melanogenesis can be rescued by activation of the canonical Wnt pathway, consistent with the critical roles of gp96 in chaperoning W nt‐coreceptor LRP 6. Thus, this work uncovered the essential role of gp96 in regulating melanogenesis.