Furin interacts with proMT1-MMP and integrin alphaV at specialized domains of renal cell plasma membrane.
Matrix metalloproteinases (MMPs) and integrins are essential for cell and extracellular matrix homeostasis. Both membrane type-1 MMP (MT1-MMP) and the integrin alphaV subunit are fully activated upon cleavage at a furin recognition site. Furin is shuttled to the cell surface through the trans-Golgi network and endosomal system, and its only known role on plasma membrane consists in activation of opportunistic pathogenic entities. Here, we report findings about the interaction of furin with MT1-MMP and the integrin alphaV at the cell surface. By using in vivo gene delivery, western blotting and immunogold electron microscopy, we provide evidence of significant pools of furin and proMT1-MMP along the surface of cells lining basement membranes. Moreover, furin and integrin alphaV are frequently found associated with the slit diaphragm of renal podocytes and around endothelial fenestrations. ProMT1-MMP, by contrast, is concentrated at the slit diaphragm. Coimmunoprecipitations and double immunogold labelings indicate that furin interacts with proMT1-MMP and alphaV at points of insertion of the slit diaphragm. Our results suggest that these focalized complexes could trigger basement membrane proteolysis either directly by activation of proMT1-MMP or indirectly by promoting activation of proMMP2.
Mayer
Gaétan
G
Department of Pathology and Cell Biology, Université de Montréal, Montreal, Quebec, H3C 3J7, Canada.
Boileau
Guy
G
Bendayan
Moïse
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D045683:Furin / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D039564:Integrin alphaV / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D004792:Enzyme Precursors; D039564:Integrin alphaV; D011994:Recombinant Proteins; D045683:Furin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases