Reference Report

Reference
Citation	Wirtz-Peitz, F., Nishimura, T., Knoblich, J.A. (2008). Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell 135(1): 161--173. (Export to RIS)
FlyBase ID	FBrf0206088
Publication Type	Research paper
PubMed ID	18854163
PubMed Abstract	Drosophila neural precursor cells divide asymmetrically by segregating the Numb protein into one of the two daughter cells. Numb is uniformly cortical in interphase but assumes a polarized localization in mitosis. Here, we show that a phosphorylation cascade triggered by the activation of Aurora-A is responsible for the asymmetric localization of Numb in mitosis. Aurora-A phosphorylates Par-6, a regulatory subunit of atypical protein kinase C (aPKC). This activates aPKC, which initially phosphorylates Lethal (2) giant larvae (Lgl), a cytoskeletal protein that binds and inhibits aPKC during interphase. Phosphorylated Lgl is released from aPKC and thereby allows the PDZ domain protein Bazooka to enter the complex. This changes substrate specificity and allows aPKC to phosphorylate Numb and release the protein from one side of the cell cortex. Our data reveal a molecular mechanism for the asymmetric localization of Numb and show how cell polarity can be coupled to cell-cycle progression.
DOI	10.1016/j.cell.2008.07.049
Related Publication(s)
Supplementary material	Supplemental Data. [FBrf0211096]
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Secondary IDs
Language of Publication	English
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Publication Type	Journal
Abbreviation	Cell
Title	Cell
Publication Year	1974-
ISBN/ISSN	0092-8674
Data from Reference
Alleles (32)
	aPKC^{CAAXWT.Scer\UAS} aPKC^ΔN.Scer\UAS aur³⁷ aur^87Ac-3 aur^Scer\UAS.cWa Avic\GFP^baz-CC01941 baz::par-6^Scer\UAS.cWa baz⁴ baz^GD1384 baz^Scer\UAS.cKa baz^{Scer\UAS.P\T.T:Avic\GFP} His2A^{Scer\UAS.T:Disc\RFP} insc^Scer\UAS.cKa l(2)gl¹ l(2)gl^{3A.Scer\UAS.T:Avic\GFP-S65T} l(2)gl^{3A.Scer\UAS.T:Hsap\MYC} l(2)gl⁴ l(2)gl^Scer\UAS.cBa l(2)gl^{Scer\UAS.T:Avic\GFP-S65T} l(2)gl^{Scer\UAS.T:Disc\RFP-mCherry} l(2)gl^{Scer\UAS.T:Hsap\MYC} l(2)gl^ts3 numb¹⁵ numb^{fl.Scer\UAS.T:Hsap\MYC} numb^S52F par-6^+tPa par-6^S34A par-6^{T:Avic\GFP-EGFP} par-6^Δ226 pon^{LD.Scer\UAS.T:Avic\GFP} Scer\GAL4^insc-Mz1407 Scer\GAL4^neur-P72
Constructs (12)
	P{par-6.EGFP} P{par-6.S34A} P{par-6^+tPa} P{UAS-baz::par-6.W} P{UAS-His-RFP} P{UAS-l(2)gl.3A.GFP.S65T} P{UAS-l(2)gl.3A.Myc} P{UAS-l(2)gl.GFP.S65T} P{UAS-l(2)gl.Myc} P{UAS-l(2)gl.RFP} P{UASp-baz.GFP} P{UAS-pon.GFP.LD}
Genes (16)
	AP-2α aPKC aur Avic\GFP baz baz::par-6 His2A His3 insc l(2)gl mira numb par-6 pon pros Scer\GAL4
Insertions (3)
	P{GAL4}neur^P72 P{GawB}insc^Mz1407 P{PTT-GC}baz^CC01941