Apoptosis and Compensatory Proliferation Signaling Are Coupled by CrkI-Containing Microvesicles

Kajal H. Gupta, Josef W. Goldufsky, Stephen J. Wood, Nicholas J. Tardi, Gayathri S. Moorthy, Douglas Z. Gilbert, Janet P. Zayas, Eunsil Hahm, Mehmet M. Altintas, Jochen Reiser, Sasha H. Shafikhani

Research output: Contribution to journalArticlepeer-review

Abstract

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. Apoptotic cells can induce proliferation in neighboring cells, a process known as compensatory proliferation. Gupta, Goldufsky, Wood et al. now show that a fraction of apoptotic cells produce and release CrkI-containing microvesicles, distinct from exosomes and apoptotic bodies, that stimulate proliferation in bystander cells upon contact.

Original languageEnglish (US)
Pages (from-to)674-684.e5
JournalDevelopmental cell
Volume41
Issue number6
DOIs
StatePublished - Jun 19 2017
Externally publishedYes

Keywords

  • ACPS
  • ACPSV
  • CT10 regulator of kinase I
  • CrkI
  • ExoT
  • Exotoxin T
  • JNK
  • NTS
  • Pseudomonas aeruginosa
  • apoptosis
  • apoptotic compensatory proliferation signaling
  • apoptotic compensatory proliferation signaling vesicle
  • c-Jun amino-terminal kinase
  • glomerulonephritis
  • nephritis
  • nephrotoxic serum

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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