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Publication : RAB6 GTPase regulates mammary secretory function by controlling the activation of STAT5.

First Author  Cayre S Year  2020
Journal  Development Volume  147
Issue  19 PubMed ID  32895290
Mgi Jnum  J:297064 Mgi Id  MGI:6471618
Doi  10.1242/dev.190744 Citation  Cayre S, et al. (2020) RAB6 GTPase regulates mammary secretory function by controlling the activation of STAT5. Development 147(19):dev190744
abstractText  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; Rab6a (F/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.
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