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Vol. 15, Issue 10, 4735-4748, October 2004
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Is Required for Actin Dynamics in Caenorhabditis elegans and Acts via Functionally Different Actin-binding Repeats



* Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University and Medical Protein Research, Flanders Interuniversity Institute for Biotechnology, Ghent, Belgium;
Department of Pathology, Emory University, Atlanta, GA 30322
Submitted March 17, 2004;
Accepted July 9, 2004
Monitoring Editor: David Drubin
Generating specific actin structures via controlled actin polymerization is a prerequisite for eukaryote development and reproduction. We here report on an essential Caenorhabditis elegans protein tetraThymosin
expressed in developing neurons and crucial during oocyte maturation in adults. TetraThymosin
has four repeats, each related to the actin monomer-sequestering protein thymosin
4 and assists in actin filament elongation. For homologues with similar multirepeat structures, a profilin-like mechanism of ushering actin onto filament barbed ends, based on the formation of a 1:1 complex, is proposed to underlie this activity. We, however, demonstrate that tetraThymosin
binds multiple actin monomers via different repeats and in addition also interacts with filamentous actin. All repeats need to be functional for attaining full activity in various in vitro assays. The activities on actin are thus a direct consequence of the repeated structure. In containing both G- and F-actin interaction sites, tetraThymosin
may be reminiscent of nonhomologous multimodular actin regulatory proteins implicated in actin filament dynamics. A mutation that suppresses expression of tetraThymosin
is homozygous lethal. Mutant organisms develop into adults but display a dumpy phenotype and fail to reproduce as their oocytes lack essential actin structures. This strongly suggests that the activity of tetraThymosin
is of crucial importance at specific developmental stages requiring actin polymerization.
Abbreviations used: CMC, critical monomer concentration; EDC, 1-ethyl-3(3-dimethylaminopropyl)carbodiimide; RU, response unit; SPR, surface plasmon resonance; T
4, thymosin
4; tT
, tetraThymosin
; WH, WASP homology; WT, wild type.
Corresponding author. E-mail address: leen.vantroys{at}ugent.be.
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