A novel role for fibronectin type I domain in the regulation of human hematopoietic cell adhesiveness through binding to follistatin domains of FLRG and follistatin.
FLRG and follistatin belong to the family of follistatin proteins involved in the regulation of various biological effects, such as hematopoiesis, mediated by their binding to activin and BMP, both members of the TGFbeta family. To further characterize the function of FLRG, we searched for other possible functional partners using a yeast two-hybrid screen. We identified human fibronectin as a new partner for both FLRG and follistatin. We also demonstrated that their physical interaction is mediated by type I motifs of fibronectin and follistatin domains. We then analyzed the biological consequences of these protein interactions on the regulation of hematopoiesis. For the first time, we associated a biological effect with the regulation of human hematopoietic cell adhesiveness of both the type I motifs of fibronectin and the follistatin domains of FLRG and follistatin. Indeed, we observed a significant and specific dose-dependent increase of cell adhesion to fibronectin in the presence of FLRG or follistatin, using either a human hematopoietic cell line or primary cells. In particular, we observed a significantly increased adhesion of immature hematopoietic precursors (CFC, LTC-IC). Altogether these results highlight a new mechanism by which FLRG and follistatin regulate human hematopoiesis.
Maguer-Satta
Véronique
V
INSERM U590, Centre Léon Bérard, Université Claude Bernard Lyon I, Lyon, 69373 Lyon Cedex 08, France. maguer@lyon.fnclcc.fr
Forissier
Stéphanie
S
Bartholin
Laurent
L
Martel
Sylvie
S
Jeanpierre
Sandrine
S
Bachelard
Elodie
E
Rimokh
Ruth
R
D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D038681:Follistatin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D038702:Follistatin-Related Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D020798:Two-Hybrid System Techniques
D005353:Fibronectins; D038681:Follistatin; D038702:Follistatin-Related Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins