title: The apicobasal polarity kinase aPKC functions as a nuclear determinant and regulates cell proliferation and fate during Xenopus primary neurogenesis.
abstract: During neurogenesis in Xenopus, apicobasally polarised superficial and non-polar deep cells take up different fates: deep cells become primary neurons while superficial cells stay as progenitors. It is not known whether the proteins that affect cell polarity also affect cell fate and how membrane polarity information may be transmitted to the nucleus. Here, we examine the role of the polarity components, apically enriched aPKC and basolateral Lgl2, in primary neurogenesis. We report that a membrane-tethered form of aPKC (aPKC-CAAX) suppresses primary neurogenesis and promotes cell proliferation. Unexpectedly, both endogenous aPKC and aPKC-CAAX show some nuclear localisation. A constitutively active aPKC fused to a nuclear localisation signal has the same phenotypic effect as aPKC-CAAX in that it suppresses neurogenesis and enhances proliferation. Conversely, inhibiting endogenous aPKC with a dominant-negative form that is restricted to the nucleus enhances primary neurogenesis. These observations suggest that aPKC has a function in the nucleus that is important for cell fate specification during primary neurogenesis. In a complementary experiment, overexpressing basolateral Lgl2 causes depolarisation and internalisation of superficial cells, which form ectopic neurons when supplemented with a proneural factor. These findings suggest that both aPKC and Lgl2 affect cell fate, but that aPKC is a nuclear determinant itself that might shuttle from the membrane to the nucleus to control cell proliferation and fate; loss of epithelial cell polarity by Lgl2 overexpression changes the position of the cells and is permissive for a change in cell fate.
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester, UK.
authors.forename: Nitin
authors.initials: N
authors.lastname: Sabherwal
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsutsui
authors.forename: Sarah
authors.initials: S
authors.lastname: Hodge
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chalmers
authors.forename: Nancy
authors.initials: N
authors.lastname: Papalopulu
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000502:physiology*; D016764:Cell Polarity; D049109:Cell Proliferation; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D014404:Tubulin; D029867:Xenopus Proteins; D028961:beta Karyopherins; C424163:late gestation lung 2 karyopherin; C101907:neurogenin, Xenopus; C095970:MYT1 kinase, Xenopus; C115015:PKC-3 protein