Interaction of secreted factor Agr2 with its potential receptors from the family of three-finger proteins

Eroshkin, Fedor M.; Martynova, Natalia Y.; Bayramov, A. V.; Ermakova, Galina V.; Ivanova, A. S.; Korotkova, Daria D.; Zaraisky, Andrey G.

doi:10.1134/s1068162017030049

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…Interestingly, Agr2 with a mutation of cysteine in the PDI motif was unable to do so ( Grassme et al, 2016 ). The interaction of Agr2 with the structural and functional homolog of Prod1, Tfp4, was also shown in Xenopus laevis ( Eroshkin et al, 2017 ). We demonstrated that Tfp4 is expressed at a low level in the ectoderm of tadpole tail and limb buds, but its expression significantly increased in the regenerative epithelium already on the 1st day after the amputation of these appendages ( Tereshina et al, 2019 ).…”

Section: Introductionmentioning

confidence: 86%

The Secreted Protein Disulfide Isomerase Ag1 Lost by Ancestors of Poorly Regenerating Vertebrates Is Required for Xenopus laevis Tail Regeneration

Ivanova

Tereshina

Araslanova

et al. 2021

Front. Cell Dev. Biol.

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Warm-blooded vertebrates regenerate lost limbs and their parts in general much worse than fishes and amphibians. We previously hypothesized that this reduction in regenerative capability could be explained in part by the loss of some genes important for the regeneration in ancestors of warm-blooded vertebrates. One of such genes could be ag1, which encodes secreted protein disulfide isomerase of the Agr family. Ag1 is activated during limb and tail regeneration in the frog Xenopus laevis tadpoles and is absent in warm-blooded animals. The essential role of another agr family gene, agr2, in limb regeneration was demonstrated previously in newts. However, agr2, as well as the third member of agr family, agr3, are present in all vertebrates. Therefore, it is important to verify if the activity of ag1 lost by warm-blooded vertebrates is also essential for regeneration in amphibians, which could be a further argument in favor of our hypothesis. Here, we show that in the Xenopus laevis tadpoles in which the expression of ag1 or agr2 was artificially suppressed, regeneration of amputated tail tips was also significantly reduced. Importantly, overexpression of any of these agrs or treatment of tadpoles with any of their recombinant proteins resulted in the restoration of tail regeneration in the refractory period when these processes are severely inhibited in normal development. These findings demonstrate the critical roles of ag1 and agr2 in regeneration in frogs and present indirect evidence that the loss of ag1 in evolution could be one of the prerequisites for the reduction of regenerative ability in warm-blooded vertebrates.

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Section: Introductionmentioning

confidence: 86%

The Secreted Protein Disulfide Isomerase Ag1 Lost by Ancestors of Poorly Regenerating Vertebrates Is Required for Xenopus laevis Tail Regeneration

Ivanova

Tereshina

Araslanova

et al. 2021

Front. Cell Dev. Biol.

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“…In our previous work, we have cloned cDNAs of 6 three‐fingers proteins, named Tfp1‐6, which are expressed during the Xenopus laevis embryogenesis, and tested their ability to form complexes with Agr2 in the co‐immunoprecipitation assay (Eroshkin et al, ). Among the tested proteins, Tfp4 demonstrated strongest affinity to Agr2 and therefore it was selected for further studying in depth.…”

Section: Introductionmentioning

confidence: 99%

“…In our previous work, we have cloned cDNAs of 6 three-fingers proteins, named Tfp1-6, which are expressed during the Xenopus laevis embryogenesis, and tested their ability to form complexes with Agr2 in the co-immunoprecipitation assay (Eroshkin et al, 2017).…”

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confidence: 99%

Agr2‐interacting Prod1‐like protein Tfp4 from Xenopus laevis is necessary for early forebrain and eye development as well as for the tadpole appendage regeneration

Tereshina

Ivanova

Eroshkin

et al. 2019

Genesis

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Summary The Agr family genes, Ag1, Agr2, and Agr3, encode for the thioredoxin domain containing secreted proteins and are specific only for vertebrates. These proteins are attracting increasing attention due to their involvement in many physiological and pathological processes, including exocrine secretion, cancer, regeneration of the body appendages, and the early brain development. At the same time, the mode by which Agrs regulate intracellular processes are poorly understood. Despite that the receptor to Agr2, the membrane anchored protein Prod1, has been firstly discovered in Urodeles, and it has been shown to interact with Agr2 in the regenerating limb, no functional homologs of Prod1 were identified in other vertebrates. This raises the question of the mechanisms by which Agrs can regulate regeneration in other lower vertebrates. Recently, we have identified that Tfp4 (three‐fingers Protein 4), the structural and functional homolog of Prod1 in Anurans, interacts with Agr2 in Xenopus laevis embryos. In the present work we show by several methods that the activity of Tfp4 is essential for the tadpole tail regeneration as well as for the early eye and forebrain development during embryogenesis. These data show for the first time the common molecular mechanism of regeneration regulation in amphibians by interaction of Prod1 and Agr2 proteins.

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The cytoskeletal protein Zyxin interacts with the zinc-finger transcription factor Zic1 and plays the role of a scaffold for Gli1 and Zic1 interactions during early development of Xenopus laevis

Martynova

Parshina

Ermolina

et al. 2018

Biochemical and Biophysical Research Communications

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Interaction of secreted factor Agr2 with its potential receptors from the family of three-finger proteins

Cited by 3 publications

References 11 publications

The Secreted Protein Disulfide Isomerase Ag1 Lost by Ancestors of Poorly Regenerating Vertebrates Is Required for Xenopus laevis Tail Regeneration

The Secreted Protein Disulfide Isomerase Ag1 Lost by Ancestors of Poorly Regenerating Vertebrates Is Required for Xenopus laevis Tail Regeneration

Agr2‐interacting Prod1‐like protein Tfp4 from Xenopus laevis is necessary for early forebrain and eye development as well as for the tadpole appendage regeneration

The cytoskeletal protein Zyxin interacts with the zinc-finger transcription factor Zic1 and plays the role of a scaffold for Gli1 and Zic1 interactions during early development of Xenopus laevis

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