Drosophila Follistatin Exhibits Unique Structural Modifications and Interacts with Several TGF-beta Family Members

Overview

Journal Mech Dev

Publisher Elsevier

Specialties Biology
Cell Biology
Reproductive Medicine

Date 2007 Dec 14

PMID 18077144

Citations 10

Authors

Daniela Bickel

Ripal Shah

Scott C Gesualdi

Theodor E Haerry

Affiliations

Soon will be listed here.

Abstract

Follistatin (FS) is one of several secreted proteins that modulate the activity of TGF-beta family members during development. The structural and functional analysis of Drosophila Follistatin (dFS) reveals important differences between dFS and its vertebrate orthologues: it is larger, more positively charged, and proteolytically processed. dFS primarily inhibits signaling of Drosophila Activin (dACT) but can also inhibit other ligands like Decapentaplegic (DPP). In contrast, the presence of dFS enhances signaling of the Activin-like protein Dawdle (DAW), indicating that dFS exhibits a dual function in promoting and inhibiting signaling of TGF-beta ligands. In addition, FS proteins may also function in facilitating ligand diffusion. We find that mutants of daw are rescued in significant numbers by expression of vertebrate FS proteins. Since two PiggyBac insertions in dfs are not lethal, it appears that the function of dFS is non-essential or functionally redundant.

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References

Rooke H, Crosier K . The smad proteins and TGFbeta signalling: uncovering a pathway critical in cancer. Pathology. 2001; 33(1):73-84. View

Matzuk M, Lu N, Vogel H, Sellheyer K, Roop D, Bradley A . Multiple defects and perinatal death in mice deficient in follistatin. Nature. 1995; 374(6520):360-3. DOI: 10.1038/374360a0. View

Ho T, Bristol L, Coccia C, Li Y, Milbrandt J, Johnson E . TGFbeta trophic factors differentially modulate motor axon outgrowth and protection from excitotoxicity. Exp Neurol. 2000; 161(2):664-75. DOI: 10.1006/exnr.1999.7290. View

Haerry T, Khalsa O, OConnor M, Wharton K . Synergistic signaling by two BMP ligands through the SAX and TKV receptors controls wing growth and patterning in Drosophila. Development. 1998; 125(20):3977-87. DOI: 10.1242/dev.125.20.3977. View

James D, Levine A, Besser D, Hemmati-Brivanlou A . TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development. 2005; 132(6):1273-82. DOI: 10.1242/dev.01706. View

Khokha M, Yeh J, Grammer T, Harland R . Depletion of three BMP antagonists from Spemann's organizer leads to a catastrophic loss of dorsal structures. Dev Cell. 2005; 8(3):401-11. DOI: 10.1016/j.devcel.2005.01.013. View

Inouye S, Ling N, Shimasaki S . Localization of the heparin binding site of follistatin. Mol Cell Endocrinol. 1992; 90(1):1-6. DOI: 10.1016/0303-7207(92)90094-m. View

Beattie G, Lopez A, Bucay N, Hinton A, Firpo M, King C . Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers. Stem Cells. 2005; 23(4):489-95. DOI: 10.1634/stemcells.2004-0279. View

Schneyer A, Wang Q, Sidis Y, Sluss P . Differential distribution of follistatin isoforms: application of a new FS315-specific immunoassay. J Clin Endocrinol Metab. 2004; 89(10):5067-75. DOI: 10.1210/jc.2004-0162. View

10.

Canalis E, Economides A, Gazzerro E . Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev. 2003; 24(2):218-35. DOI: 10.1210/er.2002-0023. View

11.

Thompson T, Lerch T, Cook R, Woodruff T, Jardetzky T . The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding. Dev Cell. 2005; 9(4):535-43. DOI: 10.1016/j.devcel.2005.09.008. View

12.

Muller B, Hartmann B, Pyrowolakis G, Affolter M, Basler K . Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient. Cell. 2003; 113(2):221-33. DOI: 10.1016/s0092-8674(03)00241-1. View

13.

MASON E, Konrad K, Webb C, Marsh J . Dorsal midline fate in Drosophila embryos requires twisted gastrulation, a gene encoding a secreted protein related to human connective tissue growth factor. Genes Dev. 1994; 8(13):1489-501. DOI: 10.1101/gad.8.13.1489. View

14.

McCabe B, Marques G, Pejmun Haghighi A, Fetter R, Crotty M, Haerry T . The BMP homolog Gbb provides a retrograde signal that regulates synaptic growth at the Drosophila neuromuscular junction. Neuron. 2003; 39(2):241-54. DOI: 10.1016/s0896-6273(03)00426-4. View

15.

Taghert P, Hewes R, Park J, OBrien M, Han M, Peck M . Multiple amidated neuropeptides are required for normal circadian locomotor rhythms in Drosophila. J Neurosci. 2001; 21(17):6673-86. PMC: 6763108. View

16.

Abe Y, Minegishi T, Leung P . Activin receptor signaling. Growth Factors. 2004; 22(2):105-10. DOI: 10.1080/08977190410001704688. View

17.

Wodarz A, Hinz U, Engelbert M, Knust E . Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell. 1995; 82(1):67-76. DOI: 10.1016/0092-8674(95)90053-5. View

18.

YASUO H, Lemaire P . Generation of the germ layers along the animal-vegetal axis in Xenopus laevis. Int J Dev Biol. 2001; 45(1):229-35. View

19.

Newfeld S, Wisotzkey R, Kumar S . Molecular evolution of a developmental pathway: phylogenetic analyses of transforming growth factor-beta family ligands, receptors and Smad signal transducers. Genetics. 1999; 152(2):783-95. PMC: 1460638. DOI: 10.1093/genetics/152.2.783. View

20.

Shimmi O, Umulis D, Othmer H, OConnor M . Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo. Cell. 2005; 120(6):873-86. PMC: 6460932. DOI: 10.1016/j.cell.2005.02.009. View