CED-1, CED-7, and TTR-52 Regulate Surface Phosphatidylserine Expression on Apoptotic and Phagocytic Cells

Mapes, James; Chen, Yu-Zen; Kim, Anna; Mitani, Shohei; Kang, Byung-Ho; Xue, Ding

doi:10.1016/j.cub.2012.05.052

Cited by 76 publications

(100 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, PS exposure was detected not only on the membranes of apoptotic cells but also on those of engulfing cells (Mapes et al 2012;Zhang et al 2012). Externalized PS appears early on the surface of the dying cells and decreases in older or unengulfed apoptotic cells.…”

Section: Surface Ps Expression On Phagocytesmentioning

confidence: 96%

“…The ABC transporter CED-7 has been proposed to mediate PS exposure in somatic apoptotic cells using the MFG-E8::GFP PS sensor (Venegas and Zhou 2007). However, multiple studies using other PS sensors show that CED-7 does not promote PS externalization in apoptotic cells (Zullig et al 2007;Mapes et al 2012;Zhang et al 2012), and instead, plays a role in the efflux of PS from apoptotic cells (Mapes et al 2012;Zhang et al 2012). …”

Section: Presentation Of Eat Me Signalsmentioning

confidence: 99%

“…Externalization of PS on the cell surface is a hallmark of apoptosis; exposed PS is a conserved eat me signal that triggers phagocytosis in many organisms, including C. elegans (Fadeel and Xue 2009). Using a secreted PS-binding protein GFP fusion such as the Annexin V::GFP fusion (sAnxV::GFP), the MFG-E8::GFP, or the secreted GFP::lactadherin fusion (sGFP::Lact C1C2 ) as a PS sensor; exposed PS is detected on the surface of apoptotic cells in C. elegans (Fadok et al 2001;Venegas and Zhou 2007;Wang et al 2007;Zullig et al 2007;Mapes et al 2012;Zhang et al 2012).…”

Section: Presentation Of Eat Me Signalsmentioning

confidence: 99%

See 2 more Smart Citations

Programmed Cell Death DuringCaenorhabditis elegansDevelopment

Conradt

Xue

2016

Genetics

Self Cite

View full text Add to dashboard Cite

Programmed cell death is an integral component of Caenorhabditis elegans development. Genetic and reverse genetic studies in C. elegans have led to the identification of many genes and conserved cell death pathways that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular, cell biological, and biochemical studies have revealed the underlying mechanisms that control these three phases of programmed cell death. In particular, the interplay of transcriptional regulatory cascades and networks involving multiple transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 and, in some cases, the ced-3 gene in cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED-4, and CED-3 results in the activation of the key cell death protease CED-3, which is tightly controlled by multiple positive and negative regulators. The activation of the CED-3 caspase then initiates the cell disassembly process by cleaving and activating or inactivating crucial CED-3 substrates; leading to activation of multiple cell death execution events, including nuclear DNA fragmentation, mitochondrial elimination, phosphatidylserine externalization, inactivation of survival signals, and clearance of apoptotic cells. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general.KEYWORDS Caenorhabditis elegans; activation phase; execution phase; programmed cell death; specification phase; WormBook

show abstract

Section: Surface Ps Expression On Phagocytesmentioning

confidence: 96%

Section: Presentation Of Eat Me Signalsmentioning

confidence: 99%

Section: Presentation Of Eat Me Signalsmentioning

confidence: 99%

See 1 more Smart Citation

Programmed Cell Death DuringCaenorhabditis elegansDevelopment

Conradt

Xue

2016

Genetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…TTR‐52 may act as an extracellular bridging molecule that mediates the binding and recognition of apoptotic cells 60. In addition, TTR‐52, together with CED‐7/ABCA1 (a plasma membrane ABC transporter that also colocalizes around apoptotic corpses), regulates exoplasmic PS expression in apoptotic cells and promotes the generation of extracellular PS vesicles that will lead to the appearance of exoplasmic PS on phagocytes, a process that facilitate cell corpse clearance 61.…”

Section: Ced‐10/rac Is At the Core Of The Phagocytosis Of Apoptotic Cmentioning

confidence: 99%

Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

et al. 2016

View full text Add to dashboard Cite

Small GTPases in the Rho family act as major nodes with functions beyond cytoskeletal rearrangements shaping the Caenorhabditis elegans embryo during development. These small GTPases are key signal transducers that integrate diverse developmental signals to produce a coordinated response in the cell. In C. elegans, the best studied members of these highly conserved Rho family small GTPases, RHO‐1/RhoA, CED‐10/Rac, and CDC‐42, are crucial in several cellular processes dealing with cytoskeletal reorganization. In this review, we update the functions described for the Rho family small GTPases in spindle orientation and cell division, engulfment, and cellular movements during C. elegans embryogenesis, focusing on the Rho subfamily Rac.Please also see the video abstract here

show abstract

“…To further confirm that TTR-52 was indeed binding to PS in this context, we analyzed the localization of a secreted version of Annexin V (sAnxV), a highly efficient and specific calcium-dependent PS binding protein [30][31][32] . PS was rapidly exposed on the proximal and distal PLM axon segments following axotomy, with sAnxV binding to both segments within 15 minutes after transection (Fig.…”

Section: Axonal Fusion During Regeneration Requires Conserved Componentsmentioning

confidence: 99%

The cellular and molecular mechanisms of axonal maintenance and regeneration

Coakley¹

View full text Add to dashboard Cite

How a neuron responds to and withstands injury is a central question in neurobiology. Neuronal injury can be caused mechanically with force, chemically with toxic insults, or genetically with mutations in genes that lead to damage. The axon, the neuron's longest compartment, is often the focal point of degeneration due to traumatic injury, toxic insults, or neurodegenerative diseases.Damage to the axon can have drastic functional consequences for the organism. In some cases axonal injury can lead to death of the neuron, while in others repair mechanisms are triggered that promote regeneration of the injured axon. Important discoveries during the last decade have uncovered many components of the molecular machinery that regulate axonal degeneration and regeneration. However, the precise ways in which these pathways converge and respond to different insults remains largely unknown. Here, using the nematode Caenorhabditis elegans as an experimental model system, we present important discoveries outlining the cellular and molecular mechanisms underpinning axonal maintenance and regeneration. Using forward and reverse genetic approaches, combined with optogenetic, genetic, and laser-injury tools, we identify critical components of these biological processes. We demonstrate how genes functioning during axon development also have roles in mature axons, regulating both degeneration and regeneration.Firstly, we discover a role for MEC-7/β-tubulin in regulating both axon development and regeneration. Second, we develop and characterize an optogenetic method to induce cell ablation and neurodegeneration using the genetically encoded photosensitizer KillerRed. Third, we identify novel mutants with defects in axonal maintenance and describe a new phenomenon of neuronal fusion following genetically induced damage. Finally, we demonstrate a role for conserved components of the apoptotic machinery in the recognition of damaged neurons during regeneration.These findings both extend our understanding of the molecular mechanisms of axonal degeneration and regeneration, as well as provide new paradigms in which these processes can be investigated.

show abstract

CED-1, CED-7, and TTR-52 Regulate Surface Phosphatidylserine Expression on Apoptotic and Phagocytic Cells

Cited by 76 publications

References 42 publications

Programmed Cell Death DuringCaenorhabditis elegansDevelopment

Programmed Cell Death DuringCaenorhabditis elegansDevelopment

Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

The cellular and molecular mechanisms of axonal maintenance and regeneration

Contact Info

Product

Resources

About