Anti-RAB6A (C-terminal) polyclonal antibody

The small GTPase Rab6 regulates vesicle trafficking at the level of Golgi. Recently, the crystal structures of Rab6 in complexes with two unrelated effectors have been determined. The structure of Rab6a-GTP in complex with a 378-residue internal fragment of the effector Rab6IP1 (Rab6-interacting protein 1) has been solved. in addition, the structure of Rab6 with the golgin, GCC185, has also been determined. in both complexes, two alpha-helices from the effector mediate binding to switch I, switch II and the interswitch region of Rab6. Comparisons of the complexes reveal significant conformational changes in the conserved hydrophobic triad of Rab6. Thus conformational flexibility in the triad mediates recognition of compositionally distinct alpha-helical coiled coils, providing a rationale for the promiscuity of Rab6 in effector recruitment.

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.