Murine Adseverin (D5), a Novel Member of the Gelsolin Family, and Murine Adseverin Are Induced by Interleukin-9 in T-Helper Lymphocytes

ABSTRACT

We identified a number of upregulated genes by differential screening of interleukin-9-stimulated T-helper lymphocytes. Interestingly, two of these messengers encode proteins that are similar to proteins of the gelsolin family. The first displays a typical structure of six homologous domains and shows a high level of identity (90%) with bovine adseverin (or scinderin) and may therefore be considered the murine adseverin homolog. The second encodes a protein with only five segments. Sequence comparison shows that most of the fifth segment and a short amino-terminal part of the sixth segment (amino acids 528 to 628 of adseverin) are missing, and thus, this form may represent an alternatively spliced product derived from the same gene. The corresponding protein is called mouse adseverin (D5). We expressed both proteins in Escherichia coli and show that mouse adseverin displays the typical characteristics of all members of the gelsolin family with respect to actin binding (capping, severing, and nucleation) and its regulation by Ca²⁺. In contrast, mouse adseverin (D5) fails to nucleate actin polymerization, although like mouse adseverin and gelsolin, it severs and caps actin filaments in a Ca²⁺-dependent manner. Adseverin is present in all of the tissues and most of the cell lines tested, although at low concentrations. Mouse adseverin (D5) was found only in blood cells and in cell lines derived from T-helper lymphocytes and mast cells, where it is weakly expressed. In a gel filtration experiment, we demonstrated that mouse adseverin forms a 1:2 complex with G actin which is stable only in the presence of Ca²⁺, while no stable complex was observed for mouse adseverin (D5).

ACKNOWLEDGMENTS

We are grateful to Caroline-Aurore Seghers for help with fluorescence experiments.

J.C.R. is a Research Associate and J.L. is a Scientific Associate (Televie) with the Fonds National de la Recherche Scientifique, Belgium. C.A. is a Research Associate of the Flanders Fund for Scientific Research (FWO). This work was supported in part by the Flanders Action for Biotechnology (VLAB-COT), the Action Levenslijn 7.0040.94, GOA 91/96-3 to J.V., and in part by the Belgian Federal Service for Scientific, Technical and Cultural Affairs and the Operation Televie.