RAB6 GTPase regulates mammary secretory function by controlling the activation of STAT5.
RAB6 GTPase regulates mammary secretory function by controlling the activation of STAT5.
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RAB6 GTPase通过控制STAT5的激活来调节乳腺分泌功能。
DOI：
10.1242/dev.190744
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发表时间：
2020-10-08
期刊：
影响因子：
--
通讯作者：
Goud B
中科院分区：
文献类型：
--
作者：
Cayre S;Faraldo MM;Bardin S;Miserey-Lenkei S;Deugnier MA;Goud B
与高尔基体相关的RAB GTP酶RAB6A和RAB6A‘调节高尔基体的顺行和逆行运输途径。在体外，RAB6A/A‘调控多种细胞功能，包括细胞分裂、迁移、黏附和极性。然而，它们在体内的作用仍然没有得到很好的描述。在这里，我们产生了BlgCre；Rab6aF/F小鼠，在怀孕和哺乳期间，在乳房腔分泌谱系中表现出特定的Rab6a缺失。Rab6a的缺失严重损害了分泌组织的分化、成熟和维持，影响了哺乳。突变的上皮细胞显示出STAT5的活性降低，STAT5是主要由催乳素控制的产乳过程的关键调节因子。从乳腺上皮细胞系获得的数据表明，STAT5激活缺陷可能源于催乳素受体的受扰运输，改变了其膜表达和信号级联。尽管在Rab6a缺失时观察到了主要的功能缺陷，但乳腺上皮双层的极化组织被保留了下来。综上所述，我们的数据揭示了RAB6A/A‘在乳腺的产乳功能中的关键作用，并表明由RAB6A/A’控制的转运途径取决于细胞类型的特化和组织环境。摘要：本研究揭示了高尔基体相关RAB GTP酶RAB6A/A‘在乳腺泌乳功能中的作用。
The Golgi-associated RAB GTPases, RAB6A and RAB6A′, regulate anterograde and retrograde transport pathways from and to the Golgi. In vitro, RAB6A/A′ control several cellular functions including cell division, migration, adhesion and polarity. However, their role remains poorly described in vivo. Here, we generated BlgCre; Rab6aF/F mice presenting a specific deletion of Rab6a in the mammary luminal secretory lineage during gestation and lactation. Rab6a loss severely impaired the differentiation, maturation and maintenance of the secretory tissue, compromising lactation. The mutant epithelium displayed a decreased activation of STAT5, a key regulator of the lactogenic process primarily governed by prolactin. Data obtained with a mammary epithelial cell line suggested that defective STAT5 activation might originate from a perturbed transport of the prolactin receptor, altering its membrane expression and signaling cascade. Despite the major functional defects observed upon Rab6a deletion, the polarized organization of the mammary epithelial bilayer was preserved. Altogether, our data reveal a crucial role for RAB6A/A′ in the lactogenic function of the mammary gland and suggest that the trafficking pathways controlled by RAB6A/A′ depend on cell-type specialization and tissue context. Summary: This study reveals a role for the Golgi-associated RAB GTPases RAB6A/A′ in the lactogenic function of the mammary gland.