The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index; 2 of the 41 sources its claims cite were checked for support.
SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis
Open accessAbstract
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 approximately 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.
Overview
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Written from the paper’s full text.
TL;DR
SLC24A5 encodes NCKX5, a potassium-dependent sodium-calcium exchanger that is partially localized to the trans-Golgi network in human epidermal melanocytes and is required for melanin synthesis. The skin-color-associated nsSNP rs1426654 changes a conserved residue and reduces NCKX5/NCKX2 exchange activity.
Key findings
- SLC24A5 was the predominant sodium-calcium exchanger transcript in cultured human and mouse melanocytes, >100-fold more highly expressed than any other SLC24A transcript; SLC8 family transcripts were not detected.
- Native NCKX5 ran as a ~43-kDa triplet on SDS-PAGE, partially co-localized with the trans-Golgi marker TGN46, showed no plasma membrane staining, and co-fractionated with TGN46 and pigment/TYRP1-enriched fractions.
- SLC24A5 knockdown reduced melanin production: 87.7% in mouse B16 melanocytes (p < 0.0001), 22% and 30.5% in NHM with siRNA 185 and 492 (p < 0.0001), and 80–90% in re-differentiating melanoblasts (p < 0.0001); melanosomal markers pmel17, MART1, TYR, and TYRP1 were reduced, while LAMP-1 increased.
- NCKX5 showed K+-dependent Na+/Ca2+ exchange activity, and the threonine-encoding allele at NCKX5 residue 111 or the equivalent NCKX2 residue 177 caused substantially reduced exchanger activity.
Methods
- Cultured normal human melanocytes (NHM), B16 F10 mouse melanoma cells, HEK293 cells, and High Five insect cells were used with real-time PCR, immunoblotting, immunofluorescence confocal microscopy, sucrose density gradient fractionation, and melanin assays.
- SLC24A5 was knocked down with siRNA duplexes in B16 and NHM, including de-differentiated melanoblasts; melanin was normalized to protein and analyzed by ANOVA with Dunnett’s adjustment.
- NCKX2 and NCKX5 mutants were expressed in High Five cells, and reverse exchange was measured as K+-dependent 45Ca2+ uptake in Na+-loaded cells.
Limitations
- The paper states that the unique intracellular localization of NCKX5 necessitated new assays because current methodologies were not suitable for measuring intracellular sodium-calcium exchange activity, and NCKX5 activity in the heterologous system was low.
- The paper states that it cannot rule out a cryptic melanosomal localization for NCKX5, that the identity of the punctate staining was not determined, and that no co-localization between NCKX5 and melanosomal markers was detected by immunofluorescence.
- Evident from the text: the NHM total-melanin knockdown effect was modest (22–30.5%), and the anti-NCKX5 antisera showed some nonspecific reactivity on Western blots.
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Claims the paper makes
35 Own result · 26 Not checked yet · 18 Own interpretation · 4 Own method · 3 No basis given · 2 Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Using data from the human HapMap project (8), they observed that the alternate alleles of the nsSNP (rs1426654) in human SLC24A5 were present at very different frequencies in populations of African and European ancestry.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > Abstract
What the sources say
- Supportedcites [8] Consortium, 2005, Nature source
The citation identifies the human HapMap project as the source of the data, and this paper reports its Phase I data. Table 9 lists rs1426654 in SLC24A5 among high-differentiation non-synonymous SNPs; the Phase I HapMap section identifies the Yoruba (YRI) and Utah (CEU) sample panels. (LLM, conf=0.88)
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In the paper
“In cultured human epidermal melanocytes we show using affinity-purified antisera that native human NCKX5 runs as a triplet of ϳ43 kDa on SDS-PAGE and is partially localized to the trans-Golgi network.”
- Also stated in: § NCKX5 Protein Is Located in an Intracellular · boosted
“Western blots of cell extracts harvested 5 days after transfection and probed with affinity-purified anti-NCKX5-(C) sera showed that a triplet of bands of ϳ43 kDa were clearly detected in extracts from control or untreated cells but were virtually absent in extracts from SLC24A5 siRNA-treated cells (Fig. 2A).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > Abstract
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- Also stated in: § NCKX5 Protein Is Located in an Intracellular · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In cultured human epidermal melanocytes we show using affinity-purified antisera that native human NCKX5 runs as a triplet of ϳ43 kDa on SDS-PAGE and is partially localized to the trans-Golgi network.”
- Also stated in: § NCKX5 Protein Is Located in an Intracellular · plain
“The perinuclear staining colocalized with the trans-Golgi marker TGN46 (Fig. 2C), although merged images of serial optical sections revealed that NCKX5 only co-localized with part of the TGN (Fig. 3A).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > Abstract
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- Also stated in: § NCKX5 Protein Is Located in an Intracellular · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
- Also stated in: § SLC24A5 Knockdown Reduces Melanin Production in NHM- · plain
“Constructs carrying the threonine variant had a greatly reduced exchange activity compared with those carrying the alanine variant (Fig. 8C).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § SLC24A5 Knockdown Reduces Melanin Production in NHM- · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using a heterologous expression system, we confirm for the first time that NCKX5 possesses the predicted exchanger activity.”
- Also stated in: § SLC24A5 Knockdown Reduces Melanin Production in NHM- · boosted
“Reverse exchange of NCKX5 was only observed when extracellular K ϩ was present and no reverse exchange was observed in the presence of either extracellular Na ϩ or Li ϩ , confirming K ϩ -dependent Na ϩ /Ca 2ϩ exchange function.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § SLC24A5 Knockdown Reduces Melanin Production in NHM- · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Removal of the NCKX5 protein through small interfering RNAmediated knockdown disrupts melanogenesis in human and murine melanocytes, causing a significant reduction in melanin pigment production.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“SLC24A5 knockdown with two different siRNA duplexes in cultured NHM reproducibly results in greater than a 20% reduction in the total normalized melanin content of these cells (Fig. 6A).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > DISCUSSION
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In the paper
“SLC24A5 mRNA Is the Predominant Sodium-Calcium Exchanger Transcript in Human and Mouse Melanocytes-In mammalian cells sodium-calcium exchange is mediated both”
- Also stated in: § SLC24A5 mRNA Is the Predominant Sodium-Calcium Exchanger Transcript in Human and Mouse Melanocytes-In mammalian cells sodium-calcium exchange is mediated both · plain
“In both cultures the predominant isoform was SLC24A5, which was Ͼ100fold more highly expressed than any of the other SLC24A transcripts, and transcripts of the SLC8 family were not detected in either cell line.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 mRNA Is the Predominant Sodium-Calcium Exchanger Transcript in Human and Mouse Melanocytes-In mammalian cells sodium-calcium exchange is mediated both
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- Also stated in: § SLC24A5 mRNA Is the Predominant Sodium-Calcium Exchanger Transcript in Human and Mouse Melanocytes-In mammalian cells sodium-calcium exchange is mediated both · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In both cultures the predominant isoform was SLC24A5, which was Ͼ100fold more highly expressed than any of the other SLC24A transcripts, and transcripts of the SLC8 family were not detected in either cell line.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 mRNA Is the Predominant Sodium-Calcium Exchanger Transcript in Human and Mouse Melanocytes-In mammalian cells sodium-calcium exchange is mediated both
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However no marked effect on the punctate staining was observed (Fig. 3C).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > NCKX5 Protein Is Located in an Intracellular
plain- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 12
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Every source the paper cites for this claim was checked and supports it.
In the paper
“The Golgi apparatus is an established calcium store (31), and its role in sorting and processing secretory and membrane proteins is highly sensitive to changes in calcium concentration within the lumen.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
- Supportedcites [31] Pinton, 1998, EMBO J. source
The Discussion describes the Golgi as “a bona fide store of rapidly mobilizable Ca²⁺” and reports agonist-dependent calcium discharge from it. This supports the cited clause that the Golgi apparatus is a calcium store. (LLM, conf=0.93)
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In the paper
“In NMH low levels of SLC24A1 and very low levels of SLC24A3 and SLC24A4 were detected, and in the mouse melanocytes, low levels of SLC24A4 and very low levels of SLC24A1 and SLC24A3 were found.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 mRNA Is the Predominant Sodium-Calcium Exchanger Transcript in Human and Mouse Melanocytes-In mammalian cells sodium-calcium exchange is mediated both
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Constructs carrying the threonine variant had a greatly reduced exchange activity compared with those carrying the alanine variant (Fig. 8C).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Knockdown Reduces Melanin Production in NHM-
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A similar pattern of staining was observed in both light and dark NHM, although the perinuclear staining was less intense in lighter melanocytes.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > NCKX5 Protein Is Located in an Intracellular
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The apparent size of these bands is surprisingly low compared with the predicted molecular mass in the absence of glycosylation of 54.9 kDa.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > NCKX5 Protein Is Located in an Intracellular
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reverse exchange of NCKX5 was only observed when extracellular K ϩ was present and no reverse exchange was observed in the presence of either extracellular Na ϩ or Li ϩ , confirming K ϩ -dependent Na ϩ /Ca 2ϩ exchange function.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Knockdown Reduces Melanin Production in NHM-
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, when SLC24A5 is disrupted through siRNA knockdown, melanosomal maturation is blocked, leading to a down-regulation of pmel17 and late melanosomal markers TYR and TYRP1.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
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In the paper
“Subsequent analyses have pinpointed this SNP and another in the SLC45A2 gene as participants in the evolution of light skin in Europeans but not East Asians (9 -11).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“De-glycosylation of the recombinant protein (Fig. 2B) removes the upper band, suggesting that the lower bands reflect signal peptide cleavage of unglycosylated protein.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > NCKX5 Protein Is Located in an Intracellular
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Conversely, expression of the lysosomal marker LAMP-1 was up-regulated after SLC24A5 knockdown, suggesting that SLC24A5 plays a role very early in melanosome biogenesis and that this process is intimately linked with lysosome biogenesis.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Knockdown Reduces Melanin Production in NHM-
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This might account for the reduced tyrosinase activity measured in Caucasian compared with Negroid-derived melanocytes (30).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
- Not checked yetcites [30] Iozumi, 1993, J. Investig. Dermatol. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data also support the hypothesis that the nsSNP associated with skin color variation is causative, directly mediating phenotypic variation in skin color by altering NCKX5 exchanger activity.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
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In the paper
“These data, supporting an intracellular, partial TGN localization, are surprising since all other NCKX proteins have been shown to traffic to the plasma membrane where they operate to remove Ca 2ϩ from the cytoplasm to the extracellular space (26 -28).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The NCKX family currently consists of five members (NCKX 1-5) that are thought to use both the inward sodium gradient and the outward potassium gradient to extrude calcium across the plasma membrane.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > Abstract
What the sources say
- Not checked yetcites [12] Altimimi, 2007, Channels source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The 85-kDa form of pmel17 that is down-regulated by SLC24A5 knockdown is a marker of early melanosomes (25), whereas Lamp1 is enriched in lysosomes (47).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
- Not checked yetcites [47] Raposo, 2001, J. Cell Biol. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, the Na ϩ /H ϩ exchanger NHE7 is located in the TGN and post-Golgi vesicles (35,36) and is differentially expressed in light and dark NHM (37) melanosomal pH could also be applied to the TGN.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Ca 2ϩ is also a co-factor for phenylalanine hydroxylase (45); the latter has been suggested to protect the redox balance and prevent DNA damage (46).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
- Not checked yetcites [45] Schallreuter, 1999, Biochem. Biophys. Res. Commun. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Endosomal membrane fusion events, which are essential processes in melanosome and lysosome-related organelle biogenesis, are Ca 2ϩ -mediated (49, 50) and are likely modulated by changing local Ca 2ϩ gradients.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
- Not checked yetcites [49] Mayorga, 1994, J. Cell Biol.
- Not checked yetcites [50] Pryor, 2000, J. Cell Biol. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In the model proposed by Raposo et al. (47,48), the coated endosome (also referred to as a stage 1 melanosome) serves as a critical sorting point between endocytic and pre-melanosomal pathways, from which macromolecules are specifically directed into melanosomal or lysosomal pathways.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this model NCKX5 is required for the correct delivery of melanosomal components such as pmel17 into the melanosomal pathway.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“The importance of correctly regulating such intracellular trafficking mechanisms to melanogenesis is highlighted by the de-pigmenting effects of certain tricyclic compounds that elicit the mis-trafficking of tyrosinase leading to its co-localization with Lamp1 (51).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
- Not checked yetcites [51] Ni-Komatsu, 2007, J. Investig. Dermatol.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent work has shown that the calcium concentration of the Golgi compartment is highly regulated in keratinocytes (32,33), and the calcium gradients across the Golgi play a fundamental part in intracellular calcium signaling and homeostasis (for review, see Ref. 34).”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We, therefore, propose a second model in which NCKX5 modulates melanogenesis through a role in the trafficking/sorting decisions, which occur within the coated endosome.”
§ SLC24A5 Encodes a trans-Golgi Network Protein with Potassium-dependent Sodium-Calcium Exchange Activity That Regulates Human Epidermal Melanogenesis * > SLC24A5 Plays a Key Role in Melanogenesis-In vivo epidermal melanocytes synthesize melanin within specialized
hedgeddirect- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true.
The paper relies on this without support.
The exchanger activity of NCKX5 has not yet been experimentally demonstrated.
“Although SLC24A5 is predicted to encode an NCKX protein, the exchanger activity of NCKX5 has yet to be experimentally demonstrated.”
The paper relies on this without support.
NCKX5's credentials as a sodium-calcium-potassium exchanger had not previously been established experimentally.
“However, despite a high degree of similarity at the amino acid level (Fig. 8B), the credentials of NCKX5 as a sodium-calcium-potassium exchanger have not previously been established experimentally.”
The paper relies on this without support.
Currently available methodologies are not suitable for measuring intracellular sodium-calcium exchange activity.
“The unique intracellular localization of NCKX5 necessitates the development of new assays as the currently available methodologies are not suitable for measuring intracellular sodium-calcium exchange activity.”
The paper relies on this without support.
The more alkaline environment of Negroid melanosomes favors the activity of tyrosinase.
“The more alkaline environment of Negroid melanosomes is believed to favor the activity of tyrosinase, a rate-limiting catalyst of melanin synthesis that operates optimally at neutral pH.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The involvement of NCKX5 in this process is highly likely given the role of this family of proteins in transmembrane Ca 2 þ transport (Schnetkamp, 2004), and the higher ion exchange activity of NCKX5-111A compared to NCKX5-111T (Ginger et al., 2008).”
From Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci (2009) · cites this paper as Ginger et al., 2008
Citations
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Metadata
- Authors
- Ginger, R. S., Askew, S. E., Ogborne, R. M., Wilson, S., Ferdinando, D., Dadd, T., Smith, A. M., Kazi, S., Szerencsei, R. T., Winkfein, R. J., Schnetkamp, P. P. M., & Green, M. R.
- Affiliations
- Unilever (United Kingdom) (GB)
- University of Calgary (CA)
- Corresponding author
- Ginger, Rebecca S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 283
- Issue
- 9
- Pages
- 5486-5495
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2109627824
- Cited by
- 158
- References
- 49
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 8 · 2020: 14 · 2019: 7 · 2018: 10 · 2017: 8 · 2016: 8 · 2015: 7 · 2014: 10 · 2013: 11 · 2012: 9
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- SLC24A5, NCKX2, Na+/Ca2+ exchanger, melanogenesis, melanocytes, trans-Golgi network, skin color variation, single nucleotide polymorphisms
- MeSH terms
- Animals, Calcium, Golgi Apparatus, Humans, Male, Melanins, Melanocytes, Pigmentation, Potassium, Sodium, Ion Transport, Antiporters, Sodium-Calcium Exchanger, Polymorphism, Single Nucleotide, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
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Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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