Evidence map›Paper›PMID 18984596›Full record

ArticleThe Journal of biological chemistry2008

A point mutation to Galphai selectively blocks GoLoco motif binding: direct evidence for Galpha.GoLoco complexes in mitotic spindle dynamics.

Francis S Willard, Zhen Zheng, Juan Guo, Gregory J Digby, Adam J Kimple, Jason M Conley, Christopher A Johnston, Dustin Bosch, Melinda D Willard, Val J Watts and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Specific inhibition of GPCR-independent G protein signaling by a rationally engineered protein.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  8. Article
  9. Article
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  11. Gαi3-Dependent Inhibition of JNK Activity on Intracellular Membranes.Frontiers in bioengineering and biotechnology · 2015
    Article
  12. Review
  13. Article
  14. Article
  15. Article
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  17. Article
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  20. AGS-3 alters Caenorhabditis elegans behavior after food deprivation via RIC-8 activation of the neural G protein G αo.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Francis S WillardDepartment of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA. willardfs@lilly.com
Zhen Zheng
Juan Guo
Gregory J Digby
Adam J Kimple
Jason M Conley
Christopher A Johnston
Dustin Bosch
Melinda D Willard
Val J Watts
Nevin A Lambert
Stephen R Ikeda
Quansheng Du
David P Siderovski
University of North Carolina at Chapel Hill · USAugusta University · USNational Institute on Alcohol Abuse and Alcoholism · USPurdue University West Lafayette · US

Funding

Neuronal Ion Channel Modulation By Second MessengersZIAAA000430 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI IKEDA, STEPHEN R · 2009 to 2017
$13.7M
D2 RECEPTOR-INDUCED SENSITIZATION OF ADENYLATE CYCLASER01MH060397 · NIMH · PURDUE UNIVERSITY WEST LAFAYETTE · PI DESSAUER, CARMEN W., WATTS, VAL J · 2000 to 2012
$3.0M
GPCR signaling complexes in living cellsR01GM078319 · NIGMS · AUGUSTA UNIVERSITY · PI LAMBERT, NEVIN ALAN · 2007 to 2017
$2.1M
Mechanisms of Mitotic Spindle Orientation in Mammalian CellsR01GM079506 · NIGMS · AUGUSTA UNIVERSITY · PI DU, QUANSHENG · 2007 to 2011
$1.3M
Mechanistic studies of a novel G-alpha nucleotide cycleR01GM074268 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SIDEROVSKI, DAVID P. · 2006 to 2009
$902k
Towards small molecule modulators of RGS proteinsF30MH074266 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIMPLE, ADAM J · 2006 to 2011
$162k
Intramural NIH HHSNIGMS NIH HHS F32 GM07694NIGMS NIH HHS GM078319NIGMS NIH HHS GM079506NIGMS NIH HHS R01 GM074268NIGMS NIH HHS R01 GM079506NIMH NIH HHS F30 MH074266NIMH NIH HHS MH060397
6 · The paper itself

Abstract

Heterotrimeric G-protein Galpha subunits and GoLoco motif proteins are key members of a conserved set of regulatory proteins that influence invertebrate asymmetric cell division and vertebrate neuroepithelium and epithelial progenitor differentiation. GoLoco motif proteins bind selectively to the inhibitory subclass (Galphai) of Galpha subunits, and thus it is assumed that a Galphai.GoLoco motif protein complex plays a direct functional role in microtubule dynamics underlying spindle orientation and metaphase chromosomal segregation during cell division. To address this hypothesis directly, we rationally identified a point mutation to Galphai subunits that renders a selective loss-of-function for GoLoco motif binding, namely an asparagine-to-isoleucine substitution in the alphaD-alphaE loop of the Galpha helical domain. This GoLoco-insensitivity ("GLi") mutation prevented Galphai1 association with all human GoLoco motif proteins and abrogated interaction between the Caenorhabditis elegans Galpha subunit GOA-1 and the GPR-1 GoLoco motif. In contrast, the GLi mutation did not perturb any other biochemical or signaling properties of Galphai subunits, including nucleotide binding, intrinsic and RGS protein-accelerated GTP hydrolysis, and interactions with Gbetagamma dimers, adenylyl cyclase, and seven transmembrane-domain receptors. GoLoco insensitivity rendered Galphai subunits unable to recruit GoLoco motif proteins such as GPSM2/LGN and GPSM3 to the plasma membrane, and abrogated the exaggerated mitotic spindle rocking normally seen upon ectopic expression of wild type Galphai subunits in kidney epithelial cells. This GLi mutation should prove valuable in establishing the physiological roles of Galphai.GoLoco motif protein complexes in microtubule dynamics and spindle function during cell division as well as to delineate potential roles for GoLoco motifs in receptor-mediated signal transduction.

Indexed as

Spindle ApparatusAmino Acid MotifsAmino Acid SequenceAnimalsCaenorhabditis elegansCell MembraneGTP-Binding Protein alpha SubunitsHumansMicrotubulesModels, MolecularMolecular Sequence DataPoint MutationRatsSequence Homology, Amino AcidSignal TransductionGTP-Binding Protein alpha Subunits

Identifiers

PMID18984596
PMCPMC2605979
OpenAlexW2034785658

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.