title: The adaptor protein Grb2 regulates cell surface Fas ligand in Schwann cells.
abstract: Fas Ligand (FasL, CD178) is a cytokine that may be secreted or expressed as a transmembrane ligand at the cell surface, and induces apoptosis by binding to the "death receptor" Fas (CD95). Here, we show that Grb2, an SH3 domain-containing adaptor protein, binds to the proline-rich domain of FasL and regulates its cell surface expression. We found that knocking down Grb2 expression decreased the amount of FasL at the cell surface and increased the abundance of intracellular vesicles containing FasL. Furthermore, we showed that Grb2 acts as an adaptor for FasL to interact with adaptin beta, a molecule known to regulate trafficking. Our data reveal that Grb2 facilitates the association of FasL with adaptin beta, and promotes sorting of FasL to the cell surface. As FasL is a potent regulator of cell death, dynamic regulation of its cell surface localization is critical for controlling local tissue remodeling and inflammation.
authors.affiliation: Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montréal, Que., Canada H3G 1Y6.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Thornhill
authors.forename: Jason B
authors.initials: JB
authors.lastname: Cohn
authors.forename: William L
authors.initials: WL
authors.lastname: Stanford
authors.forename: Julie
authors.initials: J
authors.lastname: Desbarats
mesh_terms: D033966:Adaptor Protein Complex beta Subunits / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011392:Proline / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport; D034622:RNA Interference; D012583:Schwann Cells / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D033966:Adaptor Protein Complex beta Subunits; D053222:Fas Ligand Protein; D051380:GRB2 Adaptor Protein; D011392:Proline