Functional analysis of two single nucleotide polymorphisms in SLC30A2 (ZnT2): implications for mammary gland function and breast disease in women.
Functional analysis of two single nucleotide polymorphisms in SLC30A2 (ZnT2): implications for mammary gland function and breast disease in women.
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SLC30A2 (ZnT2) 中两个单核苷酸多态性的功能分析：对女性乳腺功能和乳腺疾病的影响。
DOI：
10.1152/physiolgenomics.00137.2010
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发表时间：
2010
影响因子：
4.6
通讯作者：
Kelleher,ShannonL
中科院分区：
文献类型：
--
作者：
Seo,YoungAh;Kelleher,ShannonL
锌转运蛋白2（ZnT 2）在锌（Zn）从乳腺的输出中起主要作用。最近，我们确定，ZnT 2与分泌囊泡反映其在哺乳期锌分泌的作用。在此，我们确定了两个不同的单核苷酸多态性（SNPs）inSLC 30 A2，它编码ZnT 2。SNP 1（rs35235055）导致亮氨酸至脯氨酸的取代（Leu 23 Pro），而SNP 2（rs35623192）导致亮氨酸至半胱氨酸的取代（Arg 340 Cys）。我们研究了表达这些多态性变体的细胞中每个SNP的定位和功能。SNP 1错误定位于溶酶体，而SNP 2错误定位于高尔基体。FluoZin-3荧光显示表达SNP 1的细胞中锌的溶酶体蓄积增加，同时锌分泌消失。相反，SNP 2的异位表达与细胞质锌池的扩大、活性氧升高和锌流出增加有关。两者合计，我们的数据表明，在ZnT 2的多态性变体明显改变乳腺细胞锌代谢。我们推测这些SNPs可能会损害乳腺细胞功能，这可能对人类健康和乳腺疾病有重要意义。
Zinc transporter 2 (ZnT2) plays a major role in zinc (Zn) export from the mammary gland. Recently, we determined that ZnT2 is associated with secretory vesicles reflecting its role in Zn secretion during lactation. Herein, we identified two distinct single nucleotide polymorphisms (SNPs) inSLC30A2, which encodes ZnT2. SNP1 (rs35235055) results in a leucine-to-proline substitution (Leu23Pro), while SNP2 (rs35623192) results in an arginine-to-cysteine substitution (Arg340Cys). We examined the localization and function of each SNP in cells generated to express these polymorphic variants. SNP1 was mislocalized to lysosomes, while SNP2 was mislocalized to the Golgi apparatus. FluoZin-3 fluorescence illustrated increased lysosomal accumulation of Zn in cells expressing SNP1 concomitant with the abrogation of Zn secretion. In contrast, ectopic expression of SNP2 was associated with the expansion of cytoplasmic Zn pools, elevated reactive oxygen species, and increased Zn efflux. Taken together, our data indicate that polymorphic variants in ZnT2 distinctly alter mammary cell Zn metabolism. We speculate that these SNPs may compromise mammary cell function, which may have important implications in human health and breast disease.
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影响因子：
4
作者：
Qureshi, Omar S.;Paramasivam, Anbalakan;Murrell-Lagnado, Ruth D.
通讯作者：
Murrell-Lagnado, Ruth D.
影响因子：
3.7
作者：
Lopez, Veronica;Kelleher, Shannon L.
通讯作者：
Kelleher, Shannon L.
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
S. Thomas;L. Scott;K. Mohlke;L. Bonnycastle;C. Willer;Yun Li;W. Duren;M. Erdos;H. Stringham
通讯作者：
S. Thomas;L. Scott;K. Mohlke;L. Bonnycastle;C. Willer;Yun Li;W. Duren;M. Erdos;H. Stringham
影响因子：
4
作者：
Piccirillo, Rosanna;Palmisano, Ilaria;Schiaffino, Maria Vittoria
通讯作者：
Schiaffino, Maria Vittoria
影响因子：
4.2
作者：
Liuzzi, JP;Blanchard, RK;Cousins, RJ
通讯作者：
Cousins, RJ