Nuclear fallout provides a new link between aPKC and polarized cell trafficking

[Background]: Cell polarity, essential for cell physiology and tissue coherence, emerges as a consequence of asymmetric localization of protein complexes and directional trafficking of cellular components. Although molecules required in both processes are well known their relationship is still poorly understood. [Results]: Here we show a molecular link between Nuclear Fallout (Nuf), an adaptor of Rab11-GTPase to the microtubule motor proteins during Recycling Endosome (RE) trafficking, and aPKC, a pivotal kinase in the regulation of cell polarity. We demonstrate that aPKC phosphorylates Nuf modifying its subcellular distribution. Accordingly, in aPKC mutants Nuf and Rab11 accumulate apically indicating altered RE delivery. We show that aPKC localization in the apico-lateral cortex is dynamic. When we block exocytosis, by means of exocyst-sec mutants, aPKC accumulates inside the cells. Moreover, apical aPKC concentration is reduced in nuf mutants, suggesting aPKC levels are maintained by recycling. [Conclusions]: We demonstrate that active aPKC interacts with Nuf, phosphorylating it and, as a result, modifying its subcellular distribution. We propose a regulatory loop by which Nuf promotes aPKC apical recycling until sufficient levels of active aPKC are reached. Thus, we provide a novel link between cell polarity regulation and traffic control in epithelia.S.S. and, JM. E-V. are supported through grants of the Ministerio de Educación y Ciencia to J. C-G Hombría. This work was supported by grants of the MICINN/FEDER to J. C-G Hombría and S.S (BFU2010-15020, BFU2010-15851 and BFU2013-45866), grant of the Junta de Andalucía (P11-CVI7256) and by NIH Grants R01CA172025 to J.M., and R01CA192642 to M.T.D.-M. and 5P30CA030199 to M.T.D-M. and J.M.Peer Reviewe