The Partner of Inscuteable/Discs-Large Complex Is Required to Establish Planar Polarity during Asymmetric Cell Division in Drosophila

Bellaı̈che, Yohanns; Radovic, Anna; Woods, Daniel F.; Hough, Colleen D.; Parmentier, Marie‐Laure; O’Kane, Cahir J.; Bryant, Peter J.; Schweisguth, François

doi:10.1016/s0092-8674(01)00444-5

Cited by 220 publications

(256 citation statements)

References 53 publications

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“…To give one example, the germ line must be correctly polarized to distinguish an oocyte from supporting nurse cells, as well as to pattern the major body axes within that oocyte; neither event requires nTSG activity. Surprisingly, although all fly epithelial cells require the Scrib complex for apicobasal polarity, the Par-3 and Crumbs complexes are largely dispensable for disc epithelial architecture (Tepass and Knust 1990;Bellaiche et al 2001). It is becoming clear that the Scrib, Par-3, and Crumbs complexes are best regarded as molecular cassettes whose activities can be modified and targets altered, from tissue to tissue and from organism to organism.…”

Section: Polaritymentioning

confidence: 99%

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Bilder¹

2004

Genes Dev.

517

510

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Mammalian epithelial tumors lose polarity as they progress toward malignancy, but whether polarity loss might causally contribute to cancer has remained unclear. In Drosophila, mutations in the "neoplastic tumor suppressor genes" (nTSGs) scribble, discs-large, and lethal giant larvae disrupt polarity of epithelia and neuroblasts, and simultaneously induce extensive overproliferation of these cells, which exhibit malignant-like characteristics. Herein I review what is known about the role of the fly nTSGs in controlling cell polarity and cell proliferation. Incorporating data from mammalian studies, I consider how polarity and proliferation can be coupled, and how disruption of polarity could promote cancer.

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Section: Polaritymentioning

confidence: 99%

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Bilder¹

2004

Genes Dev.

517

510

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“…Single GPR motifs are found in Rap1GAP, Pcp2, RGS12, and RGS14, which are all implicated as G-protein regulators. Protein interaction studies and/or functional screens in yeast indicate that the AGS3 GPR motif interacts with G␣ i1-3 , but not G␣ s , G␣ q , G␣ z , G␣ 12 , or G␣ 16 (3,5,11). Specific GPR motifs are capable of interacting with G␣ o , albeit with apparently lower affinity than observed for G␣ i (10).…”

mentioning

confidence: 96%

Identification of Structural Features in the G-protein Regulatory Motif Required for Regulation of Heterotrimeric G-proteins

Peterson¹,

Hazard²,

Graber³

et al. 2002

Journal of Biological Chemistry

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The G-protein regulatory (GPR) motif, a conserved 25-30 amino acid domain found in multiple mammalian proteins, stabilizes the GDP-bound conformation of G␣ i , inhibits guanosine 5-O-(3-thiotriphosphate) (GTP␥S) binding to G␣ i and competes for G␤␥ binding to G␣. To define the core GPR motif and key amino acid residues within a GPR peptide (TMGEEDFFDLLAKSQSKRMD-DQRVDLAGThese data provide a platform for the development of novel, G-protein-selective therapeutics that inhibit G␣ imediated signaling, selectively activate G␤␥-sensitive effectors, and/or disrupt specific regulatory input to Gproteins mediated by GPR-containing proteins.The activation/deactivation cycle of heterotrimeric G-proteins, key players in cell signaling events, involves guanine nucleotide exchange, GTP hydrolysis, and a number of dynamic, conformationally sensitive protein interactions. In addition to the extensively studied activation of G-proteins by the superfamily of G-protein-coupled receptors, the G-protein activation/deactivation cycle is regulated by nonreceptor proteins that influence subunit interactions, GTPase activity, and guanine nucleotide binding properties of G␣. One signature motif for such regulatory proteins is the regulator of G-protein signaling (RGS) 1 domain, a ϳ120-amino acid motif found in all members of the RGS family (1). Another signature motif (ϳ25-30 amino acids) is defined by the G-protein regulatory (GPR) domain in activator of G-protein signaling (AGS) 3 (2-6), which was discovered in a functional screen for receptor-independent activators of G-protein signaling. The GPR motif was also recognized in RGS12 and RGS14 by general sequence analysis/alignment and termed the GoLOCO motif (7,8).Surprisingly, interaction of the GPR motif with G␣ i stabilizes the GDP bound conformation of G␣ i , competes with G␤␥ for G␣ binding, and inhibits guanine nucleotide exchange (3-6, 9 -12). Thus, the GPR motif acts as a guanine nucleotide dissociation inhibitor of G␣ i . The GPR motif is evolutionarily conserved within individual orthologs and among proteins with apparently diverse functions (see S.M.A.R.T. data base at dylan.embl-heidelberg.de/). Four spatially conserved GPR motifs are found in AGS3 (3) and LGN (13), which were isolated as G␣ i -regulatory/binding proteins. Recombinant AGS3 constructs with more than one GPR motif actually bind more than one G␣ i at the same time (5), suggesting a scaffolding role for such proteins. The AGS3/LGN-related protein PINS, which plays key roles in cell polarity (14 -17), possesses a similar domain structure. The interaction of the PINS protein GPR domains with G␣ is involved in the function of PINS in cell polarity and asymmetric cell division (17). AGS3 is also involved in synaptic adaptation in rat models of addiction (22). Single GPR motifs are found in Rap1GAP, Pcp2, RGS12, and RGS14, which are all implicated as G-protein regulators. Protein interaction studies and/or functional screens in yeast indicate that the AGS3 GPR motif interacts with G␣ i1-3 , but not G␣ s , G␣ q , G␣ z ...

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“…Inscuteable was found to control asymmetric NB divisions in association with the Partner of Inscuteable (Pins) protein and a Gα subunit (Schaefer et al 2000). In addition, Gαi and Pins, but not Inscuteable, were shown to determine the division orientation of SOP cells in Drosophila (Bellaïche et al 2001;Schaefer et al 2001). Thus, cell autonomous control of spindle positioning in the C. elegans zygote and Drosophila NB and division orientation control by planar cell polarity all turned out to use a novel form of G-protein signaling.…”

Section: Noncanonical G-protein Signalingmentioning

confidence: 99%

Polarity Control of Spindle Positioning in the C. elegans Embryo

Fielmich

Heuvel

2015

Cell Polarity 2

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Cell and tissue polarity guides a large variety of developmental processes, including the choice between symmetric and asymmetric cell division. Asymmetric divisions create cell diversity and are needed for the maintenance of tissue-specific stem cells. Symmetric divisions, on the other hand, promote exponential cell proliferation. Polarized cells often divide symmetrically by cleaving along the axis of polarity. Alternatively, cell cleavage in a plane perpendicular to the polarity axis results in asymmetric division. To control this decision, developmental cues position the mitotic spindle, which instructs the plane of cell cleavage. In animal cells, the positioning of the spindle depends on evolutionarily conserved interactions between a heterotrimeric G-protein alpha subunit, TPR-GoLoco domain protein, and NuMA-related coiled-coil protein. This trimeric complex recruits the dynein microtubule motor and captures astral microtubules at the cortex. The interplay between dynein movement and depolymerizing microtubules generates cortical pulling forces that promote aster movement and spindle positioning. Through mechanisms that are poorly understood, cell polarity and other developmental signals control the microtubule-pulling forces to instruct the orientation and plane of cell division. In this chapter, we review the current understanding of the connection between cell polarity and spindle positioning, with a focus on studies of the early C. elegans embryo. The nematode C. elegans develops through a highly reproducible division pattern and has proven to be a powerful model for studying the regulation and execution of asymmetric cell division.

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The Partner of Inscuteable/Discs-Large Complex Is Required to Establish Planar Polarity during Asymmetric Cell Division in Drosophila

Cited by 220 publications

References 53 publications

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

Identification of Structural Features in the G-protein Regulatory Motif Required for Regulation of Heterotrimeric G-proteins

Polarity Control of Spindle Positioning in the C. elegans Embryo

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