LKB1 regulates polarity remodeling and adherens junction formation in the Drosophila eye

被引:52
作者
Amin, Nancy [1 ]
Khan, Afifa [4 ]
St. Johnston, Daniel [3 ]
Tomlinson, Ian [4 ]
Martin, Sophie [3 ]
Brenman, Jay [5 ]
McNeill, Helen [1 ,2 ]
机构
[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
[2] Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A8, Canada
[3] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England
[4] Canc Res UK, Mol & Populat Genet Lab, London WC2A 3PX, England
[5] Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA
基金
芬兰科学院; 加拿大健康研究院;
关键词
AMPK; SIK; NUAK; Par-1; KP78; ACTIVATED PROTEIN-KINASE; EPITHELIAL-CELL POLARITY; C-ELEGANS EMBRYOS; PHOTORECEPTOR MORPHOGENESIS; PAR-1; KINASE; CYTOPLASMIC LOCALIZATION; GENE; POLARIZATION; BAZOOKA; CRUMBS;
D O I
10.1073/pnas.0812469106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The serine-threonine kinase LKB1 regulates cell polarity from Caenorhabditis elegans to man. Loss of lkb1 leads to a cancer predisposition, known as Peutz-Jeghers Syndrome. Biochemical analysis indicates that LKB1 can phosphorylate and activate a family of AMPK-like kinases, however, the precise contribution of these kinases to the establishment and maintenance of cell polarity is still unclear. Recent studies propose that LKB1 acts primarily through the AMP kinase to establish and/or maintain cell polarity. To determine whether this simple model of how LKB1 regulates cell polarity has relevance to complex tissues, we examined lkb1 mutants in the Drosophila eye. We show that adherens junctions expand and apical, junctional, and basolateral domains mix in lkb1 mutants. Surprisingly, we find LKB1 does not act primarily through AMPK to regulate cell polarity in the retina. Unlike lkb1 mutants, ampk retinas do not show elongated rhabdomeres or expansion of apical and junctional markers into the basolateral domain. In addition, nutrient deprivation does not reveal a more dramatic polarity phenotype in lkb1 photoreceptors. These data suggest that AMPK is not the primary target of LKB1 during eye development. Instead, we find that a number of other AMPK-like kinase, such as SIK, NUAK, Par-1, KP78a, and KP78b show phenotypes similar to weak lkb1 loss of function in the eye. These data suggest that in complex tissues, LKB1 acts on an array of targets to regulate cell polarity.
引用
收藏
页码:8941 / 8946
页数:6
相关论文
共 40 条
  • [1] Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD
    Baas, AF
    Kuipers, J
    van der Wel, NN
    Batlle, E
    Koerten, HK
    Peters, PJ
    Clevers, HC
    [J]. CELL, 2004, 116 (03) : 457 - 466
  • [2] LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons
    Barnes, Anthony P.
    Lilley, Brendan N.
    Pan, Y. Albert
    Plummer, Lisa J.
    Powell, Ashton W.
    Raines, Alexander N.
    Sanes, Joshua R.
    Polleux, Franck
    [J]. CELL, 2007, 129 (03) : 549 - 563
  • [3] Par-1 kinase establishes cell polarity and functions in Notch signaling in the Drosophila embryo
    Bayraktar, J
    Zygmunt, D
    Carthew, RW
    [J]. JOURNAL OF CELL SCIENCE, 2006, 119 (04) : 711 - 721
  • [4] Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors
    Bilder, D
    Li, M
    Perrimon, N
    [J]. SCIENCE, 2000, 289 (5476) : 113 - 116
  • [5] THE EMERGENCE OF ORDER IN THE DROSOPHILA PUPAL RETINA
    CAGAN, RL
    READY, DF
    [J]. DEVELOPMENTAL BIOLOGY, 1989, 136 (02) : 346 - 362
  • [6] The apical determinants aPKC and dPatj regulate Frizzled-dependent planar cell polarity in the Drosophila eye
    Djiane, A
    Yogev, S
    Mlodzik, M
    [J]. CELL, 2005, 121 (04) : 621 - 631
  • [7] PAR-1, A GENE REQUIRED FOR ESTABLISHING POLARITY IN C-ELEGANS EMBRYOS, ENCODES A PUTATIVE SER/THR KINASE THAT IS ASYMMETRICALLY DISTRIBUTED
    GUO, S
    KEMPHUES, KJ
    [J]. CELL, 1995, 81 (04) : 611 - 620
  • [8] SUBTYPE DETERMINATION OF DROSOPHILA EMBRYONIC EXTERNAL SENSORY ORGANS BY REDUNDANT HOMEO BOX GENES BARH1 AND BARH2
    HIGASHIJIMA, S
    MICHIUE, T
    EMORI, Y
    SAIGO, K
    [J]. GENES & DEVELOPMENT, 1992, 6 (06) : 1005 - 1018
  • [9] Distinct roles of Bazooka and Stardust in the specification of Drosophila photoreceptor membrane architecture
    Hong, Y
    Ackerman, L
    Jan, LY
    Jan, YN
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (22) : 12712 - 12717
  • [10] Drosophila Crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres
    Izaddoost, S
    Nam, SC
    Bhat, MA
    Bellen, HJ
    Choi, KW
    [J]. NATURE, 2002, 416 (6877) : 178 - 182