TY - JOUR
T1 - Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-Ptdins(3,4,5)P3 interactions
AU - Luo, Hongbo R.
AU - Huang, Yi Elaine
AU - Chen, Jianmeng C.
AU - Saiardi, Adolfo
AU - Iijima, Miho
AU - Ye, Keqiang
AU - Huang, Yunfei
AU - Nagata, Eiichiro
AU - Devreotes, Peter
AU - Snyder, Solomon H.
N1 - Funding Information:
The authors thank Tian Jin for providing the RACE cDNA library, Linnan Tang for providing anti-GFP antibody, Linfeng Chen and Chris Janetopoulos for stimulating discussions. This work was funded by USPHS grants MH-18501 to S.H.S., GM-28007 to P.N.D., and Research Scientist grant DA-00074 to S.H.S.
PY - 2003/9/5
Y1 - 2003/9/5
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(03)00640-8
DO - 10.1016/S0092-8674(03)00640-8
M3 - Article
C2 - 13678580
AN - SCOPUS:0141540848
SN - 0092-8674
VL - 114
SP - 559
EP - 572
JO - Cell
JF - Cell
IS - 5
ER -