The binding of Mss4 to α-integrin subunits regulates matrix metalloproteinase activation and fibronectin remodeling Alexander Knoblauch * , Carola Will * , Grigori Goncharenko † , Stephan Ludwig * and Viktor Wixler * ,1 * Institute of Molecular Virology, Muenster University Hospital Medical School, Muenster, Germany; and † Department of Genetics, University of Gomel, Gomel, Belarus 1 Correspondence: Institute of Molecular Virology, Muenster University Hospital Medical School, Von-Esmarch-Str. 56, 48149 Muenster, Germany. E-mail: vwixler@uni-muenster.de In four independent yeast two-hybrid screens with the integrin α-subunits α3A, α6A, α7A, and α7B, we identified the Mss4 protein, a nucleotide exchange factor for exocytic Rab GTPases, as a novel integrin interacting protein. We have previously shown that it binds to the conserved KXGFFKR region of integrin α-subunits located directly beneath the cell membrane. Here we show that the binding site for integrins on Mss4 is overlapping with those for Rab GTPases. Functional analysis of the Mss4/integrin interaction revealed its importance for activation of matrix metalloproteinases (MMPs) and remodeling of secreted extracellular matrix (ECM) proteins. The exocytosis of all the proteins analyzed, however, was unaffected. Furthermore, our data suggest that Mss4 drives the coordinated action of the MT1-MMP/integrin protein complex, thus regulating the presence and activation of MT1-MMP at newly formed filopodia and lamellipodia. This in turn facilitates the conversion of pro-MMPs to MMPs, resulting in cleavage and remodeling of ECM proteins. C2C12 myoblasts with stably down-regulated Mss4 showed a disturbed fibronectin remodeling during differentiation, resulting in malfunctioned myotube formation.—Knoblauch A., Will C., Goncharenko G., Ludwig S., Wixler V. The binding of Mss4 to α-integrin subunits regulates matrix metalloproteinase activation and fibronectin remodeling Key Words: integrin cytodomain • integrin-binding proteins • MT1-MMP • myoblast differentiation
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The binding of Mss4 to α-integrin subunits regulates matrix metalloproteinase activation and fibronectin remodeling
Knoblauch, Alexander; Will, Carola; Goncharenko, Grigori; Ludwig, Stephan; Wixler, Viktor
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, Volume 21 (2): 497
Fed of American Socs for Experimental Biology – Feb 1, 2007
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