Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par-6 in<i>Drosophila</i>neuroblast asymmetric divisions

Ogawa, Hironori; Ohta, Nao; Moon, Woongjoon; Matsuzaki, Fumio

doi:10.1242/jcs.050955

Cited by 46 publications

(44 citation statements)

References 41 publications

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“…In contrast to our observations that disruption of PTPA function in early mitosis affects localization of the Mira complex in a manner independent of aPKC, PP2A has been shown to regulate the basal localization of both the Mira and Numb complexes by antagonizing aPKC activity (Chabu and Doe, 2009;Ogawa et al, 2009;Wang et al, 2009). To investigate whether there was a correlation between PP2A activity and PTPA-mediated Mira localization during mitosis, we manipulated Mts (the catalytic subunit of PP2A) levels in the Ptpa 1 mutant background.…”

Section: Ptpa Interacts With Pp4 To Regulate Mira Localizationcontrasting

confidence: 99%

“…Furthermore, protein dephosphorylation is an important event for localization of basal proteins. Protein phosphatase 2A (PP2A) has been shown to act antagonistically to AurA to suppress aPKC signaling (Chabu and Doe, 2009;Krahn et al, 2009;Ogawa et al, 2009). Larval NBs lacking Falafel (Flfl), a regulatory subunit of Protein phosphatase 4 (PP4), exhibit defective Mira localization whereas localization of Numb remains unaffected.…”

Section: Introductionmentioning

confidence: 99%

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Phosphotyrosyl phosphatase activator facilitates Miranda localization through dephosphorylation in dividing neuroblasts

et al. 2015

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The mechanism for the basal targeting of the Miranda (Mira) complex during the asymmetric division of Drosophila neuroblasts (NBs) is yet to be fully understood. We have identified conserved Phosphotyrosyl phosphatase activator (PTPA) as a novel mediator for the basal localization of the Mira complex in larval brain NBs. In mutant Ptpa NBs, Mira remains cytoplasmic during early mitosis and its basal localization is delayed until anaphase. Detailed analyses indicate that PTPA acts independent of and before aPKC to localize Mira. Mechanistically, our data show that the phosphorylation status of the T591 residue determines the subcellular localization of Mira and that PTPA facilitates the dephosphorylation of T591. Furthermore, PTPA associates with the Protein phosphatase 4 complex to mediate localization of Mira. On the basis of these results, a two-step process for the basal localization of Mira during NB division is revealed: cortical association of Mira mediated by the PTPA-PP4 complex is followed by apical aPKC-mediated basal restriction.

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Section: Ptpa Interacts With Pp4 To Regulate Mira Localizationcontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phosphotyrosyl phosphatase activator facilitates Miranda localization through dephosphorylation in dividing neuroblasts

et al. 2015

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“…Second, other members of the protein phosphatase family, e.g. protein phosphatase 2A, are crucial regulators of cell polarity, spindle orientation and cell fate in Drosophila neural epithelium (Ogawa et al, 2009;. In this study, E14-E14.5 was used as the developmental stage of choice to analyze the behavior of distal epithelium because cell proliferation and expression of progenitor cell markers Sox9, Id2 and N-myc (Mycn -Mouse Genome Informatics) are relatively high.…”

Section: Resultsmentioning

confidence: 99%

“…Eya1 -/-distal epithelial cells exhibited a severe perturbation in the asymmetric localization and organization of several polarity proteins (Figs 2, 4 and 5; see Figs S1, S2 in the supplementary material). Similarly, members of protein phosphatase family are crucial regulators of cell polarity and spindle orientation in Drosophila epithelial cells Ogawa et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium

et al. 2011

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Cell polarity, mitotic spindle orientation and asymmetric division play a crucial role in the self-renewal/differentiation of epithelial cells, yet little is known about these processes and the molecular programs that control them in embryonic lung distal epithelium. Herein, we provide the first evidence that embryonic lung distal epithelium is polarized with characteristic perpendicular cell divisions. Consistent with these findings, spindle orientation-regulatory proteins Insc, LGN (Gpsm2) and NuMA, and the cell fate determinant Numb are asymmetrically localized in embryonic lung distal epithelium. Interfering with the function of these proteins in vitro randomizes spindle orientation and changes cell fate. We further show that Eya1 protein regulates cell polarity, spindle orientation and the localization of Numb, which inhibits Notch signaling. Hence, Eya1 promotes both perpendicular division as well as Numb asymmetric segregation to one daughter in mitotic distal lung epithelium, probably by controlling aPKCζ phosphorylation. Thus, epithelial cell polarity and mitotic spindle orientation are defective after interfering with Eya1 function in vivo or in vitro. In addition, in Eya1−/− lungs, perpendicular division is not maintained and Numb is segregated to both daughter cells in mitotic epithelial cells, leading to inactivation of Notch signaling. As Notch signaling promotes progenitor cell identity at the expense of differentiated cell phenotypes, we test whether genetic activation of Notch could rescue the Eya1−/− lung phenotype, which is characterized by loss of epithelial progenitors, increased epithelial differentiation but reduced branching. Indeed, genetic activation of Notch partially rescues Eya1−/− lung epithelial defects. These findings uncover novel functions for Eya1 as a crucial regulator of the complex behavior of distal embryonic lung epithelium.

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“…Thus, AURA is the key positive regulator of an asymmetric Numb distribution. The complex Protein Phosphatase 2A (PP2A), dephosphorylating Par-6 within the Par complex (Ogawa et al, 2009), acts as a negative regulator. The dephosphorylation excludes the possibility of aPKC activation, thereby blocking the triggering of subsequent stages in phosphorylation cascade (Fig.…”

Section: Protein Determinants Of Acdmentioning

confidence: 99%

Drosophila mechanoreceptors as a model for studying asymmetric cell division

Furman¹,

Бухарина²

2011

Int. J. Dev. Biol.

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Asymmetric cell division (ACD) is one of the processes creating the overall diversity of cell types in multicellular organisms. The essence of this process is that the daughter cells exit from it being different from both the parental cell and one another in their ability to further differentiation and specialization. The large bristles (macrochaetae) that are regularly arranged on the surface of the Drosophila adult function as mechanoreceptors, and since their development requires ACD, they have been extensively used as a model system for studying the genetic control of this process. Each macrochaete is composed of four specialized cells, the progeny resulting from several ACDs from a single sensory organ precursor (SOP) cell, which differentiates from the ectodermal cells of the wing imaginal disc in the third-instar larva and pupa. In this paper we review the experimental data on the genes and their products controlling the ACDs of the SOP cell and its daughter cells, and their further specialization. We discuss the main mechanisms determining the time when the cell enters ACD, as well as the mechanisms providing for the structural characteristics of asymmetric division, namely, polar distribution of protein determinants (Numb and Neuralized), orientation of the division spindle relative to these determinants, and unequal segregation of the determinants specifying the direction of daughter cell development.

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Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par-6 inDrosophilaneuroblast asymmetric divisions

Cited by 46 publications

References 41 publications

Phosphotyrosyl phosphatase activator facilitates Miranda localization through dephosphorylation in dividing neuroblasts

Phosphotyrosyl phosphatase activator facilitates Miranda localization through dephosphorylation in dividing neuroblasts

Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium

Drosophila mechanoreceptors as a model for studying asymmetric cell division

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