Microtubule-Mediated Inositol Lipid Signaling Plays Critical Roles in Regulation of Blebbing

PloS One
Tatsuroh SugiyamaShigehiko Yumura

Abstract

Cells migrate by extending pseudopods such as lamellipodia and blebs. Although the signals leading to lamellipodia extension have been extensively investigated, those for bleb extension remain unclear. Here, we investigated signals for blebbing in Dictyostelium cells using a newly developed assay to induce blebbing. When cells were cut into two pieces with a microneedle, the anucleate fragments vigorously extended blebs. This assay enabled us to induce blebbing reproducibly, and analyses of knockout mutants and specific inhibitors identified candidate molecules that regulate blebbing. Blebs were also induced in anucleate fragments of leukocytes, indicating that this assay is generally applicable to animal cells. After cutting, microtubules in the anucleate fragments promptly depolymerized, followed by the extension of blebs. Furthermore, when intact cells were treated with a microtubule inhibitor, they frequently extended blebs. The depolymerization of microtubules induced the delocalization of inositol lipid phosphatidylinositol 3,4,5-trisphosphate from the cell membrane. PI3 kinase-null cells frequently extended blebs, whereas PTEN-null cells extended fewer blebs. From these observations, we propose a model in which microtubu...Continue Reading

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Citations

Aug 30, 2017·Proceedings of the National Academy of Sciences of the United States of America·Thomas J LampertPeter N Devreotes
Apr 29, 2020·Cells·Md Shahabe Uddin TalukderShigehiko Yumura
May 24, 2018·Scientific Reports·Mst Shaela PervinShigehiko Yumura
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Dec 28, 2017·Genesis : the Journal of Genetics and Development·Clarissa C Pasiliao, Sevan Hopyan
Feb 17, 2019·Cell Death and Differentiation·David Guerrero-GómezAntonio Miranda-Vizuete

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Methods Mentioned

BETA
confocal microscopy
optical tweezers
GTPases

Software Mentioned

Image J

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