Apoptosis and Compensatory Proliferation Signaling Are Coupled by CrkI-Containing Microvesicles.
Apoptosis has been implicated in compensatory proliferation signaling (CPS), whereby dying cells induce proliferation in neighboring cells as a means to restore homeostasis. The nature of signaling between apoptotic cells and their neighboring cells remains largely unknown. Here we show that a fraction of apoptotic cells produce and release CrkI-containing microvesicles (distinct from exosomes and apoptotic bodies), which induce proliferation in neighboring cells upon contact. We provide visual evidence of CPS by videomicroscopy. We show that purified vesicles in vitro and in vivo are sufficient to stimulate proliferation in other cells. Our data demonstrate that CrkI inactivation by ExoT bacterial toxin or by mutagenesis blocks vesicle formation in apoptotic cells and inhibits CPS, thus uncoupling apoptosis from CPS. We further show that c-Jun amino-terminal kinase (JNK) plays a pivotal role in mediating vesicle-induced CPS in recipient cells. CPS could have important ramifications in diseases that involve apoptotic cell death.
Pubmed ID: 28633020 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Donkey Anti-Goat IgG H&L (Alexa Fluor 488) Antibody (RRID:AB_2687506)
- ALDH1A1 antibody [EP1933Y] (RRID:AB_867566)
- Donkey polyclonal Secondary Antibody to Goat IgG - H&L (HRP) (RRID:AB_10679463)
- Anti-mouse IgG, HRP-linked Antibody (RRID:AB_330924)
- Anti-rabbit IgG, HRP-linked Antibody (RRID:AB_2099233)
- CD95 antibody [UT-1] (RRID:AB_298663)
- CD9 antibody [MEM-61] (RRID:AB_302894)
- alpha Actinin 4 antibody [EPR2533(2)] (RRID:AB_10858236)
- TGF-β Antibody (RRID:AB_2063354)
- Wnt1 antibody (RRID:AB_10672669)
- Goat Anti-GFP (Green Fluorescent Protein) Polyclonal Antibody, Unconjugated (RRID:AB_304897)
- Rabbit Anti-GAPDH Antibody, Unconjugated (RRID:AB_796208)
- Phospho-SAPK/JNK (Thr183/Tyr185) (81E11) Rabbit mAb (RRID:AB_10831195)
- SAPK/JNK Antibody (RRID:AB_2250373)
- Rabbit Anti-Calreticulin Polyclonal Antibody, Unconjugated (RRID:AB_303402)
- Crk (RRID:AB_397451)
Associated grants
- Agency: NIAID NIH HHS, United States
Id: R21 AI110685
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This is a list of tools and resources that we have found mentioned in this publication.
Donkey Anti-Goat IgG H&L (Alexa Fluor 488) Antibody (antibody)
RRID:AB_2687506
This polyclonal targets Goat IgG
View all literature mentionsALDH1A1 antibody [EP1933Y] (antibody)
RRID:AB_867566
This monoclonal targets ALDH1A1
View all literature mentionsDonkey polyclonal Secondary Antibody to Goat IgG - H&L (HRP) (antibody)
RRID:AB_10679463
This polyclonal targets Donkey polyclonal Secondary to Goat IgG - H&L (HRP)
View all literature mentionsAnti-mouse IgG, HRP-linked Antibody (antibody)
RRID:AB_330924
This polyclonal targets IgG
View all literature mentionsAnti-rabbit IgG, HRP-linked Antibody (antibody)
RRID:AB_2099233
This polyclonal secondary targets IgG
View all literature mentionsCD95 antibody [UT-1] (antibody)
RRID:AB_298663
This monoclonal targets CD95 antibody [UT-1]
View all literature mentionsCD9 antibody [MEM-61] (antibody)
RRID:AB_302894
This monoclonal targets CD9
View all literature mentionsalpha Actinin 4 antibody [EPR2533(2)] (antibody)
RRID:AB_10858236
This monoclonal targets alpha Actinin 4 antibody [EPR2533(2)]
View all literature mentionsTGF-β Antibody (antibody)
RRID:AB_2063354
This polyclonal targets TGF-β Antibody
View all literature mentionsWnt1 antibody (antibody)
RRID:AB_10672669
This polyclonal targets Wnt1 antibody
View all literature mentionsGoat Anti-GFP (Green Fluorescent Protein) Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_304897
This polyclonal targets GFP
View all literature mentionsRabbit Anti-GAPDH Antibody, Unconjugated (antibody)
RRID:AB_796208
This unknown targets GAPDH
View all literature mentionsPhospho-SAPK/JNK (Thr183/Tyr185) (81E11) Rabbit mAb (antibody)
RRID:AB_10831195
This polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsSAPK/JNK Antibody (antibody)
RRID:AB_2250373
This polyclonal targets SAPK/JNK
View all literature mentionsRabbit Anti-Calreticulin Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_303402
This polyclonal targets Calreticulin
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsGraphPad Prism (software resource)
RRID:SCR_002798
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsHeLa (cell line)
RRID:CVCL_0030
Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentions
