Linking Cell Cycle to Asymmteric Division: Aurora-A phosphorylates the Par Complex to Regulate Numb ...
Download
1 / 17

Frederik Wirtz-Peitz, Takashi Nishimura and Juergen A. Knoblich Cell , 136, 161-173, 2008 - PowerPoint PPT Presentation


  • 93 Views
  • Uploaded on

Linking Cell Cycle to Asymmteric Division: Aurora-A phosphorylates the Par Complex to Regulate Numb Localization. Frederik Wirtz-Peitz, Takashi Nishimura and Juergen A. Knoblich Cell , 136, 161-173, 2008. Asymmetric cell division. Cells divide into two daughters of different fates

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Frederik Wirtz-Peitz, Takashi Nishimura and Juergen A. Knoblich Cell , 136, 161-173, 2008' - zaynah


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Linking Cell Cycle to Asymmteric Division: Aurora-A phosphorylates the Par Complex to Regulate Numb Localization

Frederik Wirtz-Peitz, Takashi Nishimura and Juergen A. Knoblich

Cell, 136, 161-173, 2008


Asymmetric cell division phosphorylates the Par Complex to Regulate Numb Localization

  • Cells divide into two daughters of different fates

  • Extrinsic and intrinsic regulation of asymmetric cell division

  • Cells segregate cell fate determinants  Numb

  • Drosophila larvael brain: balances differentiation /self renewal

Introduction


The cell fate determinant Numb phosphorylates the Par Complex to Regulate Numb Localization

  • Controls integrin endocytosis

  • Repressor of Notch signaling

  • Cell fate determinant in asymmetric cell division

     numb mutant neuroblasts divide symmetrically into two neuroblasts (Lee et al., 2006)

    Par complex provides spatial cue for Numb localization:

  • Phosphorylation by aPKC releases Numb into the cytoplasm

     Numb and aPKC localize to opposite sites of the dividing cell

www.biologie.ens.fr/desnpcs/IMG/jpg_fig2.jpg

Introduction

Introduction


Molecular mechanism for asymmetric localization of Numb during mitosis?

  • Aurora-A is required for Numb asymmetry (Berdnik and Knoblich, 2002)

  • Numb is mislocalized upon expression of Lgl3A (Betschinger et al., 2003)


AurA activates aPKC by phosphorylating during mitosis?the aPKC complex

aurA mutants:


Par6 is phosphorylated by aur a in vivo
Par6 is phosphorylated by Aur-A during mitosis?in vivo

 AurA phosphorylates Par6 in on Ser34 in vitro and in vivo


Par6 phosphorylation negatively regulates its physical interaction with apkc
Par6 phosphorylation negatively regulates its physical interaction with aPKC

 AurA activates aPKC by dissociating it from Par6


Par6 phosphorylation controls localization of numb during mitosis
Par6 phosphorylation controls localization of Numb during mitosis

 Additional substrates for AurA?


aPKC releases Lgl from the cell cortex in mitosis mitosis

Lgl is insoluble when unphosphorylated (Betschinger et al., 2003)


Aur-A is necessary and sufficient to induce mitosis cortical Lgl release


  • Numb asymmetry requiers Baz (= Par3; Bellaiche et al., 2001)


Aur-A regulates subunit composistion of the Par Complex mitosis

  • Lgl inhibits cortical localization of Baz

  • Interaction of Baz with Par6/aPKC is inhibited by Lgl

  • AurA triggers remodeling of Par complex



Exchange of Lgl for Baz enables the Par complex to phosphorylate Numb

  • Baz changes the substrate specifity of aPKC


Interaction of Numb with the Baz complex is essential for its asymmetric localization

  • numbS52F : localizes symmetrically in SOP cells can still be phosphorylated by aPKC

  • AurA induces asymmetric localization of Numb by promoting interaction of Numb with aPKC


Proposed its asymmetric localization mechanism


Summary its asymmetric localization

  • Cascade of interactions that culminate in Numb asymmetric localization

  •  Par6 is a cortical substrate for Aurora-A

  •  Par6 phosphorylation triggers exchange of Lgl for Baz in the Par complex

  •  Bax/Par complex phosphorylates Numb

  •  Restict Numb into a crescent on the opposite site

  • Lgl acts as a inhibitory subunit of the Par complex


ad