The β‐thymosins: Intracellular and extracellular activities of a versatile actin binding protein family

Abstract

The b-thymosins are N-terminally acetylated peptides of about 5 kDa molecular mass and composed of about 40-44 amino acid residues. The first member of the family, thymosin b4, was initially isolated from thymosin fraction 5, prepared in five steps from calf thymus. Thymosin b4 was supposed to be specifically produced and released by the thymic gland and to possess hormonal activities modulating the immune response. Various paracrine effects have indeed been reported for these peptides such as cardiac protection, angiogenesis, stimulation of wound healing, and hair growth. Besides these paracrine effects, it was noted that b-thymosins occur in high concentration in the cytoplasm of many eukaryotic cells and bind to the cytoskeletal component actin. Subsequently it became apparent from in vitro experiments that they preferentially bind to monomeric (G-)actin and stabilize it in its monomeric form. Due to this ability the b-thymosins are the main intracellular actin sequestering factor, i.e., they posses the ability to remove monomeric actin from the dynamic assembly and disassembly processes of the actin cytoskeleton that constantly occur in activated cells. In this review we will concentrate on the intracellular activity and localization of the b-thymosins, i.e., their modulating effect on the actin cytoskeleton. Cell Motil. Cytoskeleton 66: 839-851, 2009. '

Targeting of the actin cytoskeleton by insecticidal toxins from Photorhabdus luminescens

“…Whereas threonine-148 of actin, the TccC3-mediated ADPribosylation site, is colored in red, arginine-177 is marked in green barbed ends of actin. Therefore, thymosin-β4 inhibits actin-actin interaction at the barbed and pointed ends and is the main actin-sequestering agent in cells (Mannherz and Hannappel 2009). Cross-linking experiments reveal that ADP-ribosylation of actin at Thr-148 inhibits the interaction of actin with thymosin-β4, suggesting that TccC3 leads to a decrease in binding of thymosin-β4 to actin, which might be responsible for the enhanced polymerization of actin observed after toxin treatment (Lang et al 2010).…”

Roles of actin binding proteins in mammalian oocyte maturation and beyond

“…134 Apart from its role in monomeric actin sequestration, thymosin-b4 is involved in the regeneration and proliferation of cardiac cells 135,136 ; therefore, thymosin-b4 may play a role in early embryogenesis (e.g., cell fate specification). However, its roles in oocyte maturation and embryogenesis have not yet been investigated.…”

Microscopy ambient ionization top-down mass spectrometry reveals developmental patterning

“…β-thymosins are highly conserved polypeptides that act as actin-sequestering molecules and regulate the polymerization of G (globular) actin to form F (filamentous) actin (45)(46)(47). Altered expression of β-thymosins is strongly associated with various important biological activities, especially tissue repair and regeneration (42,43).…”