Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV

Eukaryotic chemoattraction signal transduction pathways, such as those used by Dictyostelium discoideum to move toward cAMP, use a G protein–coupled receptor to activate multiple conserved pathways such as PI3 kinase/Akt/PKB to induce actin polymerization and pseudopod formation at the front of a cell, and PTEN to localize myosin II to the rear of a cell. Relatively little is known about chemorepulsion. We previously found that AprA is a chemorepellent protein secreted by Dictyostelium cells. Here we used 29 cell lines with disruptions of cAMP and/or AprA signal transduction pathway components, and delineated the AprA chemorepulsion pathway. We find that AprA uses a subset of chemoattraction signal transduction pathways including Ras, protein kinase A, target of rapamycin (TOR), phospholipase A, and ERK1, but does not require the PI3 kinase/Akt/PKB and guanylyl cyclase pathways to induce chemorepulsion. Possibly as a result of not using the PI3 kinase/Akt/PKB pathway and guanylyl cyclases, AprA does not induce actin polymerization or increase the pseudopod formation rate, but rather appears to inhibit pseudopod formation at the side of cells closest to the source of AprA.

show abstract

“…Because there exist chemorepellents in higher eukaryotes (Herlihy et al. , 2013a, 2015, 2017; de Oliveira et al. , 2016; Nourshargh et al.…”

Section: Discussionmentioning

confidence: 99%

“…An orthologue of AprA, dipeptidyl peptidase IV (DPPIV), acts as a chemorepellent for neutrophils (Herlihy et al. , 2013a, 2015, 2017; White et al. , 2018).…”

Section: Introductionmentioning

confidence: 99%

An endogenous chemorepellent directs cell movement by inhibiting pseudopods at one side of cells

Rijal

Consalvo

Lindsey

et al. 2019

MBoC

Self Cite

View full text Add to dashboard Cite

show abstract

“…The chemorepellent AprA increased the directness of Dictyostelium cells, while DPPIV and the PAR2 agonists induced chemorepulsion without increasing directness. This suggests a difference in the chemorepulsion mechanisms used by AprA compared to the DPPIV and PAR2 agonists.…”

Section: Discussionmentioning

confidence: 94%

“…Comparatively, much less is known about the mechanisms used by cells to move away from chemorepellents . Based on initial studies on a Dictyostelium chemorepellent, we found that the human extracellular protein dipeptidyl peptidase IV (DPPIV) is a chemorepellent for human and mouse neutrophils . Since chemoattractants activate cell surface receptors, an intriguing possibility is that a neutrophil chemorepellent such as DPPIV may also activate a neutrophil cell‐surface receptor.…”

Section: Introductionmentioning

confidence: 99%

Protease activated-receptor 2 is necessary for neutrophil chemorepulsion induced by trypsin, tryptase, or dipeptidyl peptidase IV

White

Chinea

Pilling

2017

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

Compared to neutrophil chemoattractants, relatively little is known about the mechanism neutrophils use to respond to chemorepellents. We previously found that the soluble extracellular protein dipeptidyl peptidase IV (DPPIV) is a neutrophil chemorepellent. In this report, we show that an inhibitor of the protease activated receptor 2 (PAR2) blocks DPPIV-induced human neutrophil chemorepulsion, and that PAR2 agonists such as trypsin, tryptase, 2f-LIGRL, SLIGKV, and AC55541 induce human neutrophil chemorepulsion. Several PAR2 agonists in turn block the ability of the chemoattractant fMLP to attract neutrophils. Compared to neutrophils from male and female C57BL/6 mice, neutrophils from male and female mice lacking PAR2 are insensitive to the chemorepulsive effects of DPPIV or PAR2 agonists. Acute respiratory distress syndrome (ARDS) involves an insult-mediated influx of neutrophils into the lungs. In a mouse model of ARDS, aspiration of PAR2 agonists starting 24 h after an insult reduce neutrophil numbers in the bronchoalveolar lavage (BAL) fluid, as well as the post-BAL lung tissue. Together, these results indicate that the PAR2 receptor mediates DPPIV-induced chemorepulsion, and that PAR2 agonists might be useful to induce neutrophil chemorepulsion.

show abstract

“…A tertiary structure of AprA predicted by I-TASSER (Roy et al, 2010, Zhang, 2008, suggested that the AprA structure might have similarity to human dipeptidyl peptidase IV (DPPIV) (Hiramatsu et al, 2003). Both AprA and DPPIV are glycoproteins, have protease activity, and bind fibronectin (Herlihy et al, 2017). DPPIV is present in plasma and other extracellular fluids (Abbott et al, 1994, Cordero et al, 2009.…”

Section: Development Of Potential Therapeutics Based On Dictyosteliummentioning

confidence: 99%

Extracellular signaling in Dictyostelium

Consalvo

Rijal²,

Tang³

et al. 2019

Int. J. Dev. Biol.

Self Cite

View full text Add to dashboard Cite

In the last few decades, we have learned a considerable amount about how eukaryotic cells communicate with each other, and what it is the cells are telling each other. The simplicity of Dictyostelium discoideum, and the wide variety of available tools to study this organism, makes it the equivalent of a hydrogen atom for cell and developmental biology. Studies using Dictyostelium have pioneered a good deal of our understanding of eukaryotic cell communication. In this review, we will present a brief overview of how Dictyostelium cells use extracellular signals to attract each other, repel each other, sense their local cell density, sense whether the nearby cells are starving or stressed, count themselves to organize the formation of structures containing a regulated number of cells, sense the volume they are in, and organize their multicellular development. Although we are probably just beginning to learn what the cells are telling each other, the elucidation of Dictyostelium extracellular signals has already led to the development of possible therapeutics for human diseases.

show abstract

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV

Cited by 10 publications

References 41 publications

An endogenous chemorepellent directs cell movement by inhibiting pseudopods at one side of cells

An endogenous chemorepellent directs cell movement by inhibiting pseudopods at one side of cells

Protease activated-receptor 2 is necessary for neutrophil chemorepulsion induced by trypsin, tryptase, or dipeptidyl peptidase IV

Extracellular signaling in Dictyostelium

Contact Info

Product

Resources

About