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A model to die for: signaling to apoptotic cell removal in worm, fly and mouse

  • Clearance of dead cells: mechanisms, immune responses and implication in the development of diseases
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Abstract

Programmed cell death is used during developmental morphogenesis to eliminate superfluous cells or cells with inappropriate developmental potential (e.g., self-reactive immune cells, tumorigenic cells). Recent work in genetic models has led to a number of key observations, revealing signal transduction pathways and identifying new roles for genes previously studied in corpse removal (e.g., removal of broken synapses in the nervous system). Further, studies using mouse models have suggested a role for removal of apoptotic cells in the establishment or maintenance of immune tolerance. In this review, we survey current knowledge of phagocytic pathways derived from studies in the nematode (Caenorhabditis elegans), the fly (Drosophila melanogaster), and mouse (Mus musculus) model systems.

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Abbreviations

ABCA1/7:

ATP-binding cassette, sub-family A, member 1 or 7

ABL-1:

Related to oncogene Abl 1

ABI-1:

Abl interactor homologue 1

BAI1:

Brain-specific angiogenesis inhibitor-1

Ccz1:

Caffeine, calcium and zinc sensitive 1

CED (ced):

Cell death abnormal

CrkII:

v-crk Sarcoma virus CT10 oncogene homologue

Dock180:

Dedicator of cytokinesis (180 kDa), also called Dock1

DStim:

Drosophila stromal interaction molecule

DYN-1:

Dynamin related 1

ELMO:

Engulfment and cell motility

ER:

Endoplasmic reticulum

GEF:

Guanine nucleotide exchange factor

GULP:

Engulfment adapter, PTB domain containing 1

ITAM:

Immunoreceptor tyrosine-based activation motif

LXR:

Liver × receptor

LRP1:

Low density lipoprotein receptor-related protein 1

MEGF10:

Multiple EGF-like domains 10

MFG-E8:

Milk fat globule-EGF factor 8 (also called lactadherin)

MIG-2:

Abnormal cell migration 2

MOM-5:

More of MS 5

MTM-1:

MTM (myotubularin) family 1

Mon1:

Monensin sensitivity protein 1

ORAI:

ORAI calcium release-activated calcium modulator

PKC:

Protein kinase C

PPAR:

Peroxisome proliferation-activated receptor

PtdSer:

Phosphatidylserine

RABX-5:

Rab exchange factor

Rac1:

Ras-related C3 botulinum toxin substrate 1

RhoG:

Ras homologue gene family, member G

RME-6:

Receptor-mediated endocytosis 6

SAND-1:

SAND endocytosis protein family

SR-A:

Scavenger receptor, types I and II, isoform A

Syk:

Spleen tyrosine kinase

TAG-333:

Temporarily assigned gene name 333

TBC-2:

TBC (Tre-2/Bub2/Cvc16) domain family 2

TIM:

T-cell immunoglobulin and mucin domain containing

Ub:

Ubiquitin

Vps34:

Vacuolar protein sorting factor 34

UNC-73:

Uncoordinated 73

ZAP-70:

Zeta-chain (TCR) associated protein kinase (70 kDa)

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Acknowledgements

The author would like to thank K. S. Ravichandran and Cynthia Grimsley-Myers for helpful comments and discussion on this review. JMK is supported by a Scientist Development Grant from the American Heart Association and a grant from the American Cancer Society.

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  1. Department of Microbiology, Center for Cell Clearance, University of Virginia, Rm 3704A, MR-6, 345 Crispell Dr., Charlottesville, VA, 22908, USA

    Jason M. Kinchen

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Kinchen, J.M. A model to die for: signaling to apoptotic cell removal in worm, fly and mouse. Apoptosis 15, 998–1006 (2010). https://doi.org/10.1007/s10495-010-0509-5

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