Evidence map›Paper›PMID 9456322›Full record

ArticleThe Journal of cell biology1998

Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation.

J C Mills, N L Stone, J Erhardt, R N Pittman

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed
10.9field-weighted citation impact, top 1% 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

165 citing papers in PubMed, 491 citations in OpenAlex.

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  8. The concealed side of caspases: beyond a killer of cells.Cellular and molecular life sciences : CMLS · 2024
    Review
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  10. Kynurenic acid protects against ischemia/reperfusion injury by modulating apoptosis in cardiomyocytes.Apoptosis : an international journal on programmed cell death · 2024
    Article
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105 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

J C MillsDepartment of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
N L Stone
J Erhardt
R N Pittman
University of Pennsylvania · US

Funding

NEURONAL CELL DEATHR01NS032465 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI PITTMAN, RANDALL N · 1994 to 2004
$1.3M
NINDS NIH HHS NS 32465NINDS NIH HHS R01 NS032465OHS HRSA HHS MSTP 5-T32-6M07170
6 · The paper itself

Abstract

The evolutionarily conserved execution phase of apoptosis is defined by characteristic changes occurring during the final stages of death; specifically cell shrinkage, dynamic membrane blebbing, condensation of chromatin, and DNA fragmentation. Mechanisms underlying these hallmark features of apoptosis have previously been elusive, largely because the execution phase is a rapid event whose onset is asynchronous across a population of cells. In the present study, a model system is described for using the caspase inhibitor, z-VAD-FMK, to block apoptosis and generate a synchronous population of cells actively extruding and retracting membrane blebs. This model system allowed us to determine signaling mechanisms underlying this characteristic feature of apoptosis. A screen of kinase inhibitors performed on synchronized blebbing cells indicated that only myosin light chain kinase (MLCK) inhibitors decreased blebbing. Immunoprecipitation of myosin II demonstrated that myosin regulatory light chain (MLC) phosphorylation was increased in blebbing cells and that MLC phosphorylation was prevented by inhibitors of MLCK. MLC phosphorylation is also mediated by the small G protein, Rho. C3 transferase inhibited apoptotic membrane blebbing, supporting a role for a Rho family member in this process. Finally, blebbing was also inhibited by disruption of the actin cytoskeleton. Based on these results, a working model is proposed for how actin/myosin II interactions cause cell contraction and membrane blebbing. Our results provide the first evidence that MLC phosphorylation is critical for apoptotic membrane blebbing and also implicate Rho signaling in these active morphological changes. The model system described here should facilitate future studies of MLCK, Rho, and other signal transduction pathways activated during the execution phase of apoptosis.

Indexed as

ApoptosisActinsAmino Acid Chloromethyl KetonesAnimalsBloodCell MembraneCOS CellsCulture MediaCysteine Proteinase InhibitorsCytoskeletonDiacetylEnzyme InhibitorsGTP-Binding ProteinsIntracellular Signaling Peptides and ProteinsModels, BiologicalMyosin-Light-Chain KinaseActinsAmino Acid Chloromethyl Ketonesbenzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketoneCulture MediaCysteine Proteinase InhibitorsDiacetyldiacetylmonoximeEnzyme InhibitorsGTP-Binding ProteinsIntracellular Signaling Peptides and ProteinsMyosin-Light-Chain KinaseMyosin Light ChainsMyosinsProtein Serine-Threonine Kinasesrho-Associated Kinases

Identifiers

PMID9456322
PMCPMC2140178
OpenAlexW2057163366

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.