title: Nuclear fallout provides a new link between aPKC and polarized cell trafficking.
abstract: 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.
authors.affiliation: CABD, CSIC/JA/UPO, Campus Universidad Pablo de Olavide, Ctra. De Utrera Km. 1, Seville, 41013, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Calero-Cuenca
authors.affiliation: CABD, CSIC/JA/UPO, Campus Universidad Pablo de Olavide, Ctra. De Utrera Km. 1, Seville, 41013, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Espinosa-Vázquez
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Reina-Campos
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA, 92037, USA.
authors.forename: María T
authors.initials: MT
authors.lastname: Díaz-Meco
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Moscat
authors.affiliation: CABD, CSIC/JA/UPO, Campus Universidad Pablo de Olavide, Ctra. De Utrera Km. 1, Seville, 41013, Spain. ssotmar@upo.es.
authors.forename: Sol
authors.initials: S
authors.lastname: Sotillos
mesh_terms: D000818:Animals; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000032:analysis / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D060066:Protein Interaction Maps; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; C111662:nuf protein, Drosophila; C115015:PKC-3 protein; D011493:Protein Kinase C
keywords: Cell polarity; Cell trafficking; Nuclear fallout; aPKC