SLC24A5 encodes a trans-golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis

被引：110

作者：

Ginger, Rebecca S. ^{[1
]}

Askew, Sarah E. ^{[1
]}

Ogborne, Richard M. ^{[1
]}

Wilson, Stephen ^{[1
]}

Ferdinando, Dudley ^{[1
]}

Dadd, Tony ^{[1
]}

Smith, Adrian M. ^{[1
]}

Kazi, Shubana ^{[1
]}

Szerencsei, Robert T. ^{[2
]}

Winkfein, Robert J. ^{[2
]}

Schnetkamp, Paul P. M. ^{[2
]}

Green, Martin R. ^{[1
]}

机构：

[1] Unilever Res Labs Colworth, Colworth Sci Parks, Sharnbrook MK44 1LQ, Beds, England

[2] Univ Calgary, Hotchkiss Brain Inst, Dept Phys & Biophys, Calgary, AB T2N 4N1, Canada

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 09期

关键词：

D O I：

10.1074/jbc.M707521200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A non-synonymous single nucleotide polymorphism in the human SLC24A5 gene is associated with natural human skin color variation. Multiple sequence alignments predict that this gene encodes a member of the potassium-dependent sodium-calcium exchanger family denoted NCKX5. In cultured human epidermal melanocytes we show using affinity-purified antisera that native human NCKX5 runs as a triplet of similar to 43 kDa on SDS-PAGE and is partially localized to the trans-Golgi network. Removal of the NCKX5 protein through small interfering RNA-mediated knockdown disrupts melanogenesis in human and murine melanocytes, causing a significant reduction in melanin pigment production. Using a heterologous expression system, we confirm for the first time that NCKX5 possesses the predicted exchanger activity. Site-directed mutagenesis of NCKX5 and NCKX2 in this system reveals that the non-synonymous single nucleotide polymorphism in SLC24A5 alters a residue that is important for NCKX5 and NCKX2 activity. We suggest that NCKX5 directly regulates human epidermal melanogenesis and natural skin color through its intracellular potassium-dependent exchanger activity.

引用

页码：5486 / 5495

页数：10

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