Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins

Hampoelz, Bernhard; Hoeller, Oliver; Bowman, Sarah K.; Dunican, Dara J.; Knoblich, Juergen A.

doi:10.1038/ncb1318

Cited by 115 publications

(110 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is in accordance with earlier results showing that the ric-8 reduction-of-function mutants of C. elegans exhibit embryonic lethality . Moreover, Drosophila ric-8 mutants have various gastrulation defects and the homozygous ric-8 mutants die in a second instar larvae stage (Hampoelz et al, 2005;Wang et al, 2005).…”

Section: Expression Of Ric-8 During Early Embryogenesis Of Mousementioning

confidence: 99%

“…It assists in the alignment of mitotic spindle, nuclear migration, and other centrosomemediated events during early embryogenesis in C. elegans Afshar et al, 2004Afshar et al, , 2005Couwenbergs et al, 2004;Wilkie and Kinch, 2005) and in the formation of neuroblasts and sensory precursor cells in Drosophila (David et al, 2005;Hampoelz et al, 2005;Wang et al, 2005). Biochemical studies of mammalian RIC-8 function suggest that it regulates the microtubule pulling forces on centrosomes during cell division (Tall and Gilman, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies demonstrate that mammalian RIC-8 participates in the assembly of a cortical signalling complex that orients the mitotic spindle (Woodard et al, 2010). The ric-8 reduction-offunction mutants of C. elegans exhibited embryonic lethality , whereas ric-8 mutants of Drosophila had various defects during the asymmetric cell division and in gastrulation (Hampoelz et al, 2005;Wang et al, 2005). Although the crucial role of RIC-8 in the embryogenesis of C. elegans and Drosophila is appreciated, its function in mammalian embryogenesis is poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Tõnissoo¹,

Lulla²,

Meier³

et al. 2010

Developmental Dynamics

View full text Add to dashboard Cite

The guanine nucleotide exchange factor RIC-8 is a conserved protein essential for the asymmetric division in the early embryogenesis in different organisms. The function of RIC-8 in mammalian development is not characterized so far. In this study we map the expression of RIC-8 during the early development of mouse. To elucidate the RIC-8 function we used Ric-8 2/2 mutant embryos. The Ric-8 2/2 embryos reach the gastrulation stage but do not develop further and die at E6.5-E8.5. We characterized the Ric-8 2/2 embryonic phenotype by morphological and marker gene analyses. The gastrulation is initiated in Ric-8 2/2 embryos but their growth is retarded, epiblast and mesoderm disorganized. Additionally, the basement membrane is defective, amnion folding and the formation of allantois are interfered, also the cavitation. Furthermore, the orientation of the Ric-8 2/2 embryo in the uterus was abnormal. Our study reveals that the activity of RIC-8 protein is irreplaceable for the correct gastrulation of mouse embryo. Developmental Dynamics 239:3404-3415,

show abstract

Section: Expression Of Ric-8 During Early Embryogenesis Of Mousementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Tõnissoo¹,

Lulla²,

Meier³

et al. 2010

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…In addition to G protein-coupled receptor (GPCR)-mediated activation of G protein signaling, nature has evolved other modes of signal input to G proteins that either act independent of a GPCR or modulate signal transfer from receptor to G protein. Recent studies also indicate a role of G␣ and G␤␥ in the processing of signals within the cell distinct from those that they mediate following activation by a cell-surface GPCRs (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). In such situations, the G protein subunits (G␣ and G␤␥) may actually be complexed with alternative binding partners independent of the typical heterotrimeric G␣␤␥.…”

mentioning

confidence: 99%

Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with Gβγ

Sato

Cismowski

Toyota

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

As part of a broader effort to identify postreceptor signal regulators involved in specific diseases or organ adaptation, we used an expression cloning system in Saccharomyces cerevisiae to screen cDNA libraries from rat ischemic myocardium, human heart, and a prostate leiomyosarcoma for entities that activated G protein signaling in the absence of a G protein coupled receptor. We report the characterization of activator of G protein signaling (AGS) 8 (KIAA1866), isolated from a rat heart model of repetitive transient ischemia. AGS8 mRNA was induced in response to ventricular ischemia but not by tachycardia, hypertrophy, or failure. Hypoxia induced AGS8 mRNA in isolated adult ventricular cardiomyocytes but not in rat aortic smooth muscle cells, endothelial cells, or cardiac fibroblasts, suggesting a myocyte-specific adaptation mechanism involving remodeling of G protein signaling pathways. The bioactivity of AGS8 in the yeast-based assay was independent of guanine nucleotide exchange by G␣, suggesting an impact on subunit interactions. Subsequent studies indicated that AGS8 interacts directly with G␤␥ and this occurs in a manner that apparently does not alter the regulation of the effector PLC-␤ 2 by G␤␥. Mechanistically, AGS8 appears to promote G protein signaling by a previously unrecognized mechanism that involves direct interaction with G␤␥.accessory protein ͉ signal adaptation ͉ hypoxia

show abstract

“…NB asymmetric divisions are controlled by an apically localized complex of proteins that include the Drosophila homologs of the conserved Par3 (Bazooka, Baz)/Par6 (DmPar6)/atypical protein kinase C(DaPKC) proteins (Kuchinke et al 1998;Wodarz et al 2000;Petronczki and Knoblich 2001), Inscuteable (Insc) (Kraut et al 1996), and heterotrimeric G proteins G␣i (Schaefer et al 2001;Yu et al 2003) and their regulators Partner of Insc (Pins) (Yu et al 2000), Locomotion defects (Loco) , and a Pins-interacting protein mushroom body defective (Mud) (Bowman et al 2006;Izumi et al 2006;Siller et al 2006). The asymmetric localization of G␣i requires G␤ (Schaefer et al 2001;Yu et al 2003) and G␥ (Fuse et al 2003) and its membrane localization requires Ric-8 (Hampoelz et al 2005;Wang et al 2005). Basal protein localization and segregation are mediated by apical proteins through cortically localized tumor suppressors, Discs large (Dlg) and Lethal (2) giant larvae (Lgl) (Ohshiro et al 2000;Peng et al 2000).…”

mentioning

confidence: 99%

Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

Wang¹,

Somers²,

Bashirullah³

et al. 2006

Genes Dev.

246

294

View full text Add to dashboard Cite

The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Neural progenitors of the Drosophila post-embryonic brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which divides terminally to produce two differentiating neuronal/glial daughters. Here we show that Aurora-A (AurA) acts as a tumor suppressor by suppressing NB self-renewal and promoting neuronal differentiation. In aurA loss-of-function mutants, supernumerary NBs are produced at the expense of neurons. AurA suppresses tumor formation by asymmetrically localizing atypical protein kinase C (aPKC), an NB proliferation factor. Numb, which also acts as a tumor suppressor in larval brains, is a major downstream target of AurA and aPKC. Notch activity is up-regulated in aurA and numb larval brains, and Notch signaling is necessary and sufficient to promote NB self-renewal and suppress differentiation in larval brains. Our data suggest that AurA, aPKC, Numb, and Notch function in a pathway that involved a series of negative genetic interactions. We have identified a novel mechanism for controlling the balance between self-renewal and neuronal differentiation during the asymmetric division of Drosophila larval NBs.[Keywords: Neuroblast; stem cells; asymmetric division; tumor suppressor; self-renewal] Supplemental material is available at http://www.genesdev.org.

show abstract

Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins

Cited by 115 publications

References 32 publications

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Identification of a receptor-independent activator of G protein signaling (AGS8) in ischemic heart and its interaction with Gβγ

Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts

Contact Info

Product

Resources

About