Ancient Cytokines, the Role of Astakines as Hematopoietic Growth Factors

Abstract

Hematopoiesis is the process by which hemocytes mature and subsequently enter the circulation. Vertebrate prokineticins (PKs) are known to take part in this process, as are the invertebrate prokineticin domain proteins, astakines. In Pacifastacus leniusculus, astakine 1 is essential for the release of new hemocytes into the open circulatory system of these animals. In addition to astakine 1, we have now cloned a homologue of astakine 1 with an insert of 13 amino acids, named as astakine 2. Both crustacean astakines lack the N-terminal AVIT motif, which is present in vertebrate PKs, and hence receptor binding differs from that of vertebrate PKs. We have found astakine-like sequences in 19 different invertebrate species, and the sequences show that some motifs are conserved among invertebrate groups. Previously we showed that astakine 1 is directly involved in hematopoiesis, and now we show that astakine 1 and astakine 2 have different roles in hemocyte lineage differentiation. Astakine 1 can stimulate proliferation of hematopoietic tissue (Hpt) cells (precursor of hemocytes) as well as specifically induce differentiation of Hpt cells along the semigranular cell lineage, whereas astakine 2 plays a role in granular cell differentiation. Moreover, we discuss the impact of the putative structures of different astakines in comparison with the vertebrate prokineticins.

Crustacean hematopoiesis

“…Only a few proteins specific for different hemocyte types have been identified. However, some of the proteins detected in P. leniusculus have been used to identify different differentiation pathways, showing the importance of such "marker" proteins for understanding how hematopoiesis is regulated (Lin et al, 2010;Lin and Söderhäll, 2011b;Wu et al, 2008).…”

Unique diversity of the venom peptides from the scorpion Androctonus bicolor revealed by transcriptomic and proteomic analysis

“…Astakines are homologues of vertebrate prokineticins, a family of small secreted cytokines of approximately 80 amino acids, which were initially isolated from the venom of the black mamba, Dendroaspis polylepis, as a nontoxic peptide [68]. Recently, it was found that Astakines play essential roles in the hematopoiesis of invertebrates [68,69].…”

“…Recently, it was found that Astakines play essential roles in the hematopoiesis of invertebrates [68,69].…”

Invertebrate Hematopoiesis: An Astakine-Dependent Novel Hematopoietic Factor

“…A new astakine, astakine 2, was recently found in crayfish, and the two astakines were found to play different roles in the he-matopoiesis in crayfish (12). Astakine 1 can stimulate proliferation of Hpt cells and differentiation of Hpt cells along the SGC lineage both in vivo and in vitro, whereas astakine 2 plays an important role in the maturation of GCs in vivo.…”