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1.
Nat Cell Biol ; 7(11): 1083-90, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16228010

ABSTRACT

Localization and activation of heterotrimeric G proteins have a crucial role during asymmetric cell division. The asymmetric division of the Drosophila sensory precursor cell (pl) is polarized along the antero-posterior axis by Frizzled signalling and, during this division, activation of Galphai depends on Partner of Inscuteable (Pins). We establish here that Ric-8, which belongs to a family of guanine nucleotide-exchange factors for Galphai, regulates cortical localization of the subunits Galphai and Gbeta13F. Ric-8, Galphai and Pins are not necessary for the control of the anteroposterior orientation of the mitotic spindle during pl cell division downstream of Frizzled signalling, but they are required for maintainance of the spindle within the plane of the epithelium. On the contrary, Frizzled signalling orients the spindle along the antero-posterior axis but also tilts it along the apico-basal axis. Thus, Frizzled and heterotrimeric G-protein signalling act in opposition to ensure that the spindle aligns both in the plane of the epithelium and along the tissue polarity axis.


Subject(s)
Cell Division/physiology , Drosophila/metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , GTP-Binding Proteins/metabolism , Guanine Nucleotide Exchange Factors/physiology , Neurons, Afferent/physiology , Animals , Animals, Genetically Modified , Cell Cycle Proteins/metabolism , Cell Polarity , Drosophila/genetics , Drosophila Proteins/metabolism , Drosophila Proteins/physiology , Frizzled Receptors/physiology , GTP-Binding Protein beta Subunits/physiology , GTP-Binding Proteins/genetics , Spindle Apparatus/metabolism , Stem Cells/metabolism , Transforming Growth Factor beta/physiology
2.
Curr Biol ; 15(10): 955-62, 2005 May 24.
Article in English | MEDLINE | ID: mdl-15916953

ABSTRACT

Asymmetric distribution of fate determinants is a fundamental mechanism underlying the acquisition of distinct cell fates during asymmetric division. In Drosophila neuroblasts, the apical DmPar6/DaPKC complex inhibits Lethal giant larvae (Lgl) to promote the basal localization of fate determinants. In contrast, in the sensory precursor (pI) cells that divide asymmetrically with a planar polarity, Lgl inhibits Notch signaling in the anterior pI daughter cell, pIIb, by a yet-unknown mechanism. We show here that Lgl promotes the cortical recruitment of Partner of Numb (Pon) and regulates the asymmetric distribution of the fate determinants Numb and Neuralized during the pI cell division. Analysis of Pon-GFP and Histone2B-mRFP distribution in two-color movies confirmed that Lgl regulates Pon localization. Moreover, posterior DaPKC restricts Lgl function to the anterior cortex at mitosis. Thus, Lgl functions similarly in neuroblasts and in pI cells. We also show that Lgl promotes the acquisition of the pIIb cell fate by inhibiting the plasma membrane localization of Sanpodo and thereby preventing the activation of Notch signaling in the anterior pI daughter cell. Thus, Lgl regulates cell fate by controlling Pon cortical localization, asymmetric localization of Numb and Neuralized, and plasma-membrane localization of Sandopo.


Subject(s)
Carrier Proteins/metabolism , Cell Differentiation/physiology , Drosophila Proteins/metabolism , Drosophila/physiology , Signal Transduction/physiology , Stem Cells/metabolism , Tumor Suppressor Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Drosophila/metabolism , Green Fluorescent Proteins , Histones/metabolism , Immunohistochemistry , Microfilament Proteins/metabolism , Neurons/cytology , Protein Transport/physiology
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