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PMID:28388446

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Citation

Zheng, X, Chen, M, Meng, X, Chu, X, Cai, C and Zou, F (2017) Phosphorylation of dynamin-related protein 1 at Ser616 regulates mitochondrial fission and is involved in mitochondrial calcium uniporter-mediated neutrophil polarization and chemotaxis. Mol. Immunol. 87:23-32

Abstract

During an inflammatory response, polarization of neutrophils is necessary for effective chemotaxis and bacterial endocytosis. Ca(2+) uptake into mitochondria through the mitochondrial calcium uniporter (MCU) is crucial for cell metabolism, signaling and survival; however, the physiological role of MCU in human neutrophils remains unclear. Here we show that MCU is vital for the polarization and chemotaxis of neutrophils. Activation of MCU by spermine promotes neutrophil polarization and chemotaxis, whereas inhibition of MCU by Ru360 blunts both processes. We also provide evidence that this role of the MCU in neutrophils may result from modulation of mitochondrial fission by increased levels of pDrp1 S616 via accumulation of Ca(2+) into the mitochondrial matrix. Thus, our study identifies the dependence of neutrophil polarization and chemotaxis on the MCU and highlights the importance of regulating mitochondrial fission during the anti-inflammatory cascade in human neutrophils.

Links

PubMed Online version:10.1016/j.molimm.2017.03.019

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:DNM1L

GO:0090023: positive regulation of neutrophil chemotaxis

ECO:0000315:

P

Suppression of Drp1 revealed inhibition of neutrophil polarization and chemotaxis; thus, as seen in Fig. 6.Thus, Drp1 is needed for neutrophil chemotaxis. Dynamin-1-like protein (DNM1L_HUMAN) Homo sapiens (Human)

complete
CACAO 12719

HUMAN:MCU

GO:0090023: positive regulation of neutrophil chemotaxis

ECO:0000315:

P

Activation of the MCU promotes neutrophil polarization and chemotaxis; additionally, inhibition of the MCU blunted both processes, as seen on Fig. 1. Calcium uniporter protein, mitochondrial Homo sapiens (Human)

complete
CACAO 12720

HUMAN:MCU

GO:0090141: positive regulation of mitochondrial fission

ECO:0000315:

P

Figure 4 shows the effect of MCU on mitochondrial morphology, specifically indicating mitochondrial fission. Calcium uniporter protein, mitochondrial Homo sapiens (Human)

complete
CACAO 12721

HUMAN:MCU

GO:0090527: actin filament reorganization

ECO:0000315:

P

F-actin accumulation (or polymerization) at the uroprod of neutrophils during MCU-dependent chemotaxis. Observable at Fig. 2. Calcium uniporter protein, mitochondrial Homo sapiens (Human)

complete
CACAO 12722

Notes

Ru360 is a Ruthenium compound that inhibits Ca uptake in mitochondria.

See also

References

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