Thrombin stimulates wortmannin-inhibitable phosphoinositide 3-kinase and membrane blebbing in CHRF-288 cells

Vemuri, Geeta S.; Zhang, Jin; Huang, R S; Keen, James H.; Rittenhouse, Susan E.

doi:10.1042/bj3140805

Cited by 25 publications

(12 citation statements)

References 21 publications

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“…Although our experiments do not distinguish between inhibition of PtdIns 3/4-kinases, we note that low levels of LY and WT (predicted from experiments on mammalian cells to block PtdIns 3-kinase but not PtdIns 4-kinase activity) are sufficient to block cytokinesis. Further support for PtdIns 3-kinase involvement is that after washout of either LY or WT there is dramatic cellular blebbing, similar to previously reported effects of activation of PtdIns 3-kinase (Vemuri et al, 1996).…”

Section: Multiple Ptdins Steps Influence Cytokinesissupporting

confidence: 68%

Continuous phosphatidylinositol metabolism is required for cleavage of crane fly spermatocytes

Saul

Fabian

Forer

et al. 2004

Journal of Cell Science

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Successful cleavage of animal cells requires co-ordinated regulation of the actomyosin contractile ring and cleavage furrow ingression. Data from a variety of systems implicate phosphoinositol lipids and calcium release as potential regulators of this fundamental process. Here we examine the requirement for various steps of the phosphatidylinositol (PtdIns) cycle in dividing crane fly (Nephrotoma suturalis) spermatocytes. PtdIns cycle inhibitors were added to living cells after cleavage furrows formed and began to ingress. Inhibitors known to block PtdIns recycling (lithium), PtdIns phosphorylation (wortmannin, LY294002) or phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] hydrolysis [U73122 (U7)] all stopped or slowed furrowing. The effect of these drugs on cytokinesis was quite rapid (within 0-4 minutes), so continuous metabolism of PtdIns appears to be required for continued cleavage furrow ingression. U7 caused cleavage furrow regression concomitant with depletion of F-actin from the contractile ring, whereas the other inhibitors caused neither regression nor depletion of F-actin. That U7 depletes furrow-associated actin seems counterintuitive, as inhibition of phospholipase C would be expected to increase cellular levels of PtdIns(4,5)P2 and hence increase actin polymerization. Our confocal images suggest, however, that F-actin might accumulate at the poles of U7-treated cells, consistent with the idea that PtdIns(4,5)P2 hydrolysis may be required for actin filaments formed at the poles to participate in contractile ring assembly at the furrow.

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Section: Multiple Ptdins Steps Influence Cytokinesissupporting

confidence: 68%

Continuous phosphatidylinositol metabolism is required for cleavage of crane fly spermatocytes

Saul

Fabian

Forer

et al. 2004

Journal of Cell Science

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“…Membrane blebbing also occurs as a consequence of thrombin stimulation in a wortmannin-sensitive manner in CHRF-288 cells (60). Because this effect was shown to act though phosphoinositide 3-kinase, we also tested the effects of wortmannin on SP-induced blebbing and found that it occurred in a phosphatidylinositol 3-kinase-independent manner (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Neurokinin 1 Receptor Mediates Membrane Blebbing in HEK293 Cells through a Rho/Rho-associated Coiled-coil Kinase-dependent Mechanism

Meshki

Douglas

Lai

et al. 2009

Journal of Biological Chemistry

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We have investigated the effect of neurokinin 1 receptor (NK1R) agonists on HEK293 cells transfected with the NK1R receptor. The NK1R receptor mediates dramatic shape changes that include contractions of the membrane cortex resulting in membrane bleb formation. We have found that the cell shape changes correlate with changes in electrical impedance measured in cellular monolayers. The shape and impedance changes were prevented after preincubation with NK1R antagonists aprepitant and L-73060. Although bleb formation usually heralds apoptotic cell death, we have found that NK1R-mediated cellular blebbing does not associate with apoptosis. Preincubation with a cell-permeable derivative of C3 transferase that blocks Rho or with the Rho-associated coiled-coil kinase inhibitor Y27632 completely prevented NK1R-induced shape and impedance changes. Blebbing was also completely inhibited by ML-9, a myosin light chain kinase inhibitor. Furthermore, the phospholipase C inhibitor U73,122 did not interfere with the effect of Substance P (SP) on cellular morphology and cellular impedance but completely blocked SP-induced intracellular calcium increase, indicating that the blebbing is a process independent of intracellular calcium elevations. Blebbing is a protein kinase C-independent process, since the nonselective protein kinase C inhibitor GF109203X did not interfere with SP-induced effects. Based on these results, we provide the first evidence that NK1R receptorligand interaction can cause apoptosis-independent cellular blebbing and that this process is mediated by the Rho/Rho-associated coiled-coil kinase pathway.

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“…Thus, it is possible that staurosporine may antagonize either ROCK or MLCK kinase activity. Membrane blebbing in response to thrombin receptor activation has also been associated with phosphoinositide 3-kinase (Vemuri et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

The Angiotensin II Type 1 Receptor Induces Membrane Blebbing by Coupling to Rho A, Rho Kinase, and Myosin Light Chain Kinase

Godin¹,

Ferguson²

2010

Mol Pharmacol

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The angiotensin II type 1 receptor (AT 1 R) is a G␣ q/11 -coupled G protein-coupled receptor that is widely expressed in multiple tissues, including vascular smooth muscle cells, brain, and kidney. Activation of the AT 1 R in vascular smooth muscle cells leads to alterations in actin-based membrane protrusions such as lamellipodia, filopodia, and membrane blebs that ultimately lead to cell migration, which is important for the regulation of vascular tone. In the present study, we examine the role of small G proteins in mediating AT 1 R-induced alterations in membrane dynamics in human embryonic kidney 293 cells. We find that the activation of the AT 1 R with 100 nM angiotensin II results in the rapid formation of membrane blebs at early time points of agonist stimulation that cease within 40 min of agonist stimulation. AT 1 R-stimulated membrane bleb formation is independent of RalA, RalB, Rac1, cdc42, Arf6, and Ras, but it involves RhoA. Furthermore, membrane blebbing activated by the AT 1 R is attenuated in the presence of the ␤-arrestin aminoterminal domain, Ral GDP dissociation stimulator (RalGDS) ␤-arrestin binding domain, and short interfering RNA (siRNA) depletion of ␤-arrestin2. However, siRNA depletion of RalGDS protein did not affect membrane blebbing in response to AT 1 R activation. The inhibition of the downstream RhoA effectors Rho kinase (ROCK) and myosin light chain kinase (MLCK) effectively attenuated AT 1 R-mediated membrane blebbing. Thus, we show that membrane blebbing in response to AT 1 R signaling is dependent on ␤-arrestin2 and is mediated by a RhoA/ ROCK/MLCK-dependent pathway.

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Thrombin stimulates wortmannin-inhibitable phosphoinositide 3-kinase and membrane blebbing in CHRF-288 cells

Cited by 25 publications

References 21 publications

Continuous phosphatidylinositol metabolism is required for cleavage of crane fly spermatocytes

Continuous phosphatidylinositol metabolism is required for cleavage of crane fly spermatocytes

Neurokinin 1 Receptor Mediates Membrane Blebbing in HEK293 Cells through a Rho/Rho-associated Coiled-coil Kinase-dependent Mechanism

The Angiotensin II Type 1 Receptor Induces Membrane Blebbing by Coupling to Rho A, Rho Kinase, and Myosin Light Chain Kinase

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