Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-Ptdins(3,4,5)P3 interactions

Hongbo R. Luo, Yi Elaine Huang, Jianmeng C. Chen, Adolfo Saiardi, Miho Iijima, Keqiang Ye, Yunfei Huang, Eiichiro Nagata, Peter N Devreotes, Solomon H Snyder

Research output: Contribution to journalArticle

Abstract

Inositol phosphates are well-known signaling molecules, whereas the inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (InsP7/IP7) and bis-diphosphoinositol tetrakisphosphate (InsP8/IP8), are less well characterized. We demonstrate physiologic regulation of Dictyostelium chemotaxis by InsP7 mediated by its competition with PtdIns(3,4,5)P3 for binding pleckstrin homology (PH) domain-containing proteins. Chemoattractant stimulation triggers rapid and sustained elevations in InsP7/InsP8 levels. Depletion of InsP7 and InsP8 by deleting the gene for InsP6 kinase (InsP6K/IP6K), which converts inositol hexakisphosphate (InsP6/IP6) to InsP7, causes rapid aggregation of mutant cells and increased sensitivity to cAMP. Chemotaxis is mediated by membrane translocation of certain PH domain-containing proteins via specific binding to PtdIns(3,4,5)P3. InsP7 competes for PH domain binding with PtdIns(3,4,5)P3 both in vitro and in vivo. InsP7 depletion enhances PH domain membrane translocation and augments downstream chemotactic signaling activity.

Original languageEnglish (US)
Pages (from-to)559-572
Number of pages14
JournalCell
Volume114
Issue number5
DOIs
StatePublished - Sep 5 2003

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Dictyostelium
Diphosphates
Inositol
Chemotaxis
Membranes
Cell Aggregation
Phytic Acid
Inositol Phosphates
Chemotactic Factors
phosphatidylinositol 3,4,5-triphosphate
inositol heptakisphosphate
Pleckstrin Homology Domains
platelet protein P47
Proteins
Phosphotransferases
Agglomeration
Genes
Molecules

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-Ptdins(3,4,5)P3 interactions. / Luo, Hongbo R.; Huang, Yi Elaine; Chen, Jianmeng C.; Saiardi, Adolfo; Iijima, Miho; Ye, Keqiang; Huang, Yunfei; Nagata, Eiichiro; Devreotes, Peter N; Snyder, Solomon H.

In: Cell, Vol. 114, No. 5, 05.09.2003, p. 559-572.

Research output: Contribution to journalArticle

Luo, Hongbo R. ; Huang, Yi Elaine ; Chen, Jianmeng C. ; Saiardi, Adolfo ; Iijima, Miho ; Ye, Keqiang ; Huang, Yunfei ; Nagata, Eiichiro ; Devreotes, Peter N ; Snyder, Solomon H. / Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-Ptdins(3,4,5)P3 interactions. In: Cell. 2003 ; Vol. 114, No. 5. pp. 559-572.
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