TY - JOUR
T1 - Cystinosin is a melanosomal protein that regulates melanin synthesis
AU - Chiaverini, Christine
AU - Sillard, Laura
AU - Flori, Enrica
AU - Ito, Shosuke
AU - Briganti, Stefania
AU - Wakamatsu, Kazumasa
AU - Fontas, Eric
AU - Berard, Etienne
AU - Cailliez, Mathilde
AU - Cochat, Pierre
AU - Foulard, Michel
AU - Guest, Geneviève
AU - Niaudet, Patrick
AU - Picardo, Mauro
AU - Bernard, François Xavier
AU - Antignac, Corinne
AU - Ortonne, Jean Paul
AU - Ballotti, Robert
PY - 2012/9
Y1 - 2012/9
N2 - Cystinosis is a rare autosomal recessive disease characterized by cystine crystal accumulation leading to multiorgan dysfunctions and caused by mutation in CTNS. CTNS encodes cystinosin, a cystine/H+ symporter that exports cystine out of the lysosomes. Patients with cystinosis frequently exhibit blond hair and fair complexion, suggesting an alteration in melanogenesis. However, the pigmentation singularities of these patients have not been studied, and the role of cystinosin in melanogenesis has remained unknown. In our study, a clinical evaluation of 27 patients with cystinosis showed that 44% had a cutaneous pigmentation dilution compared to their relatives. Analysis of the hair melanin content in these patients by HPLC demonstrated a 50% decrease in eumelanin (4360 vs. 9360 ng/mg), and a 2-fold increase in pheomelanin (53 vs. 20 ng/mg), the yellow/red pigments. Cystinosin-deficient mice also showed a 4-fold increase in hair pheomelanin content. In vitro studies showed that cystinosin was located at melanosomes. CTNS silencing led to a 75% reduction of melanin synthesis that was caused by a degradation of tyrosinase by lysosomal proteases. Our results objectify the pigmentation defect in patients with cystinosis. We also identify the role of CTNS in melanogenesis and add a new gene to the list of the genes involved in the control of skin and hair pigmentation.
AB - Cystinosis is a rare autosomal recessive disease characterized by cystine crystal accumulation leading to multiorgan dysfunctions and caused by mutation in CTNS. CTNS encodes cystinosin, a cystine/H+ symporter that exports cystine out of the lysosomes. Patients with cystinosis frequently exhibit blond hair and fair complexion, suggesting an alteration in melanogenesis. However, the pigmentation singularities of these patients have not been studied, and the role of cystinosin in melanogenesis has remained unknown. In our study, a clinical evaluation of 27 patients with cystinosis showed that 44% had a cutaneous pigmentation dilution compared to their relatives. Analysis of the hair melanin content in these patients by HPLC demonstrated a 50% decrease in eumelanin (4360 vs. 9360 ng/mg), and a 2-fold increase in pheomelanin (53 vs. 20 ng/mg), the yellow/red pigments. Cystinosin-deficient mice also showed a 4-fold increase in hair pheomelanin content. In vitro studies showed that cystinosin was located at melanosomes. CTNS silencing led to a 75% reduction of melanin synthesis that was caused by a degradation of tyrosinase by lysosomal proteases. Our results objectify the pigmentation defect in patients with cystinosis. We also identify the role of CTNS in melanogenesis and add a new gene to the list of the genes involved in the control of skin and hair pigmentation.
KW - Cystinosis
KW - Melanocyte
KW - Melanogenesis
KW - Pigmentation
KW - Tyrosinase
UR - http://www.scopus.com/inward/record.url?scp=84865780241&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865780241&partnerID=8YFLogxK
U2 - 10.1096/fj.11-201376
DO - 10.1096/fj.11-201376
M3 - Article
C2 - 22649030
AN - SCOPUS:84865780241
VL - 26
SP - 3779
EP - 3789
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 9
ER -