Mapping the zinc-transporting system in mammary cells: molecular analysis reveals a phenotype-dependent zinc-transporting network during lactation.
Mapping the zinc-transporting system in mammary cells: molecular analysis reveals a phenotype-dependent zinc-transporting network during lactation.
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DOI：
10.1002/jcp.22900
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发表时间：
2012-04
影响因子：
5.6
通讯作者：
MacDavid, Joshua
中科院分区：
文献类型：
--
作者：
Kelleher, Shannon L.;Velasquez, Vanessa;Croxford, Thomas P.;McCormick, Nicholas H.;Lopez, Veronica;MacDavid, Joshua
在哺乳期间，乳腺上皮细胞从非分泌细胞转变为终末分化的分泌细胞。锌（Zn）是表型转变的关键调节剂，因为它调节300多种生物学功能，包括转录、翻译、能量转换、细胞内信号传导和凋亡。此外，Zn必须从正常细胞功能重定向到分泌室中，因为分泌系统的许多组分是Zn依赖性的，并且非常大量的Zn（1-3 mg Zn/d）被分泌到乳汁中。在此，我们利用了“系统生物学”的基因组和蛋白质组分析的方法来探索机制，通过该机制，锌是重新分配在哺乳期乳腺从小鼠和培养的乳腺细胞的表型转变。9种锌转运蛋白在哺乳期锌的再分配中起着关键作用。6种Zip（Zip 3、Zip 5、Zip 7、Zip 8、Zip 10、Zip 11）和3种ZnT（ZnT 2、ZnT 4、ZnT 9）蛋白质的蛋白质丰度在泌乳期间增加> 2倍，这不一定通过mRNA表达的变化来反映。我们的数据表明，Zip 5，Zip 8和Zip 10可能是从母体循环中获得锌的关键，而多种Zip蛋白从牛奶中重新摄取锌。共聚焦显微镜培养的乳腺细胞确定高尔基体（部分由ZnT 5，Zip 7和Zip 11调制）和晚期内体室（部分由ZnT 2和Zip 3调制）作为关键的细胞内隔室，通过它在哺乳期间锌被重新分配。这些结果提供了一个重要的框架，了解锌转运网络，通过乳腺锌池重新分配和分泌到牛奶。
The mammary epithelial cell transitions from a, non-secreting to a terminally differentiated, secreting cell during lactation. Zinc (Zn) is a key modulator of phenotypic transition as it regulates over 300 biological functions including transcription, translation, energy transformation, intracellular signaling and apoptosis. In addition, Zn must be redirected from normal cellular functions into the secretory compartment, as many components of the secretory system are Zn-dependant and an extraordinary amount of Zn is secreted (1–3 mg Zn/d) into milk. Herein, we utilized a “systems biology” approach of genomic and proteomic profiling to explore mechanisms through which Zn is reallocated during phenotype transition in the lactating mammary gland from mice and cultured mammary cells. Nine Zn transporters play key roles in Zn redistribution within the network during lactation. Protein abundance of six Zip (Zip3, Zip5, Zip7, Zip8, Zip10, Zip11) and three ZnT (ZnT2, ZnT4, ZnT9) proteins was expanded > 2-fold during lactation, which was not necessarily reflected by changes in mRNA expression. Our data suggest that Zip5, Zip8 and Zip10 may be key to Zn acquisition from maternal circulation, while multiple Zip proteins reuptake Zn from milk. Confocal microscopy of cultured mammary cells identified the Golgi apparatus (modulated in part by ZnT5, Zip7 and Zip11) and the late endosomal compartment (modulated in part by ZnT2 and Zip3) as key intracellular compartments through which Zn is reallocated during lactation. These results provide an important framework for understanding the Zn transporting network through which mammary gland Zn pools are redistributed and secreted into milk.
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影响因子：
4.2
作者：
Kelleher, SL;Lönnerdal, B
通讯作者：
Lönnerdal, B
影响因子：
3.3
作者：
Lemire, Joseph;Mailloux, Ryan;Appanna, Vasu D.
通讯作者：
Appanna, Vasu D.
影响因子：
6.1
作者：
Hoac, Tien;Lundh, Thomas;Akesson, Bjorn
通讯作者：
Akesson, Bjorn
影响因子：
5.3
作者：
Creamer, Bradley A.;Sakamoto, Kazuhito;Wagner, Kay-Uwe
通讯作者：
Wagner, Kay-Uwe
影响因子：
12.4
作者：
Boyle, K. B.;Hadaschik, D.;Siddle, K.
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Siddle, K.