Evidence map›Paper›PMID 23902692›Full record

ArticleJournal of cell science2013

Phosphorylation of chemoattractant receptors regulates chemotaxis, actin reorganization and signal relay.

Joseph A Brzostowski, Satoshi Sawai, Orr Rozov, Xin-Hua Liao, Daisuke Imoto, Carole A Parent, Alan R Kimmel

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

23 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Decoding the chemotactic signal.Journal of leukocyte biology · 2018
    Review
  11. Review
  12. G-Protein Dependent Signal Transduction and Ubiquitination in Dictyostelium.International journal of molecular sciences · 2017
    Review
  13. Article
  14. Article
  15. Fold-change detection and scale invariance of cell-cell signaling in social amoeba.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. Article
  17. Article
  18. Function and Regulation of Heterotrimeric G Proteins during Chemotaxis.International journal of molecular sciences · 2016
    Review
  19. Article
  20. Review
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

7 authors at 3 institutions in 2 countries.

Joseph A BrzostowskiLaboratory of Immunogenetics Imaging Facility, NIAID/NIH, Rockville, MD 20852, USA.
Satoshi Sawai
Orr Rozov
Xin-Hua Liao
Daisuke Imoto
Carole A Parent
Alan R Kimmel
National Institutes of Health · USThe University of Tokyo · JPNational Institute of Allergy and Infectious Diseases · US

Funding

SIGNALING PATHWAYS IN CONTROL OF GROWTH AND DEVELOPMENTZIADK075040 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI KIMMEL, ALAN R · 2009 to 2025
$23.9M
Signaling Events Regulating ChemotaxisZIABC010418 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PARENT, CAROLE · 2009 to 2017
$4.6M
Intramural NIH HHS
6 · The paper itself

Abstract

Migratory cells, including mammalian leukocytes and Dictyostelium, use G-protein-coupled receptor (GPCR) signaling to regulate MAPK/ERK, PI3K, TORC2/AKT, adenylyl cyclase and actin polymerization, which collectively direct chemotaxis. Upon ligand binding, mammalian GPCRs are phosphorylated at cytoplasmic residues, uncoupling G-protein pathways, but activating other pathways. However, connections between GPCR phosphorylation and chemotaxis are unclear. In developing Dictyostelium, secreted cAMP serves as a chemoattractant, with extracellular cAMP propagated as oscillating waves to ensure directional migratory signals. cAMP oscillations derive from transient excitatory responses of adenylyl cyclase, which then rapidly adapts. We have studied chemotactic signaling in Dictyostelium that express non-phosphorylatable cAMP receptors and show through chemotaxis modeling, single-cell FRET imaging, pure and chimeric population wavelet quantification, biochemical analyses and TIRF microscopy, that receptor phosphorylation is required to regulate adenylyl cyclase adaptation, long-range oscillatory cAMP wave production and cytoskeletal actin response. Phosphorylation defects thus promote hyperactive actin polymerization at the cell periphery, misdirected pseudopodia and the loss of directional chemotaxis. Our data indicate that chemoattractant receptor phosphorylation is required to co-regulate essential pathways for migratory cell polarization and chemotaxis. Our results significantly extend the understanding of the function of GPCR phosphorylation, providing strong evidence that this evolutionarily conserved mechanism is required in a signal attenuation pathway that is necessary to maintain persistent directional movement of Dictyostelium, neutrophils and other migratory cells.

Indexed as

ActinsCells, CulturedChemotaxisDictyosteliumMechanistic Target of Rapamycin Complex 2Microscopy, ConfocalMitogen-Activated Protein Kinase 1Multiprotein ComplexesPhosphatidylinositol 3-KinasesPhosphorylationProtozoan ProteinsReceptors, Cyclic AMPReceptors, G-Protein-CoupledSignal TransductionTOR Serine-Threonine KinasesActinscyclic AMP receptor cAR1Mechanistic Target of Rapamycin Complex 2Mitogen-Activated Protein Kinase 1Multiprotein ComplexesPhosphatidylinositol 3-KinasesProtozoan ProteinsReceptors, Cyclic AMPReceptors, G-Protein-CoupledTOR Serine-Threonine KinasesAKTcAMPERK2GPCRHeterotrimeric G proteinsOscillationsPI3KTORC2

Identifiers

PMID23902692
PMCPMC3795335
OpenAlexW2108374461

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.