Annexin VI binds S100A1 and S100B and blocks the ability of S100A1 and S100B to inhibit desmin and GFAP assemblies into intermediate filaments.
Annexin VI, a member of a family of Ca(2+)-dependent phospholipid- and membrane-binding proteins, interacts with the Ca(2+)-regulated EF-hand proteins, S100A1 and S100B, and blocks the ability of these two proteins to inhibit the assembly of desmin and glial fibrillary acidic protein (GFAP) into intermediate filaments in a Ca(2+)- and dose-dependent manner. S100A1 and S100B each possess one annexin VI binding site, characterized by an affinity for annexin VI in the submicromolar range. Binding of annexin VI to either S100 protein occurs at a site that appears to differ in some parts from that recognizing desmin and GFAP. As S100A1 and S100B exist in solution as homodimers in which the two monomers are related by a 2-fold symmetry axis, each of the above S100 homodimers likely crosslinks two annexin VI molecules, a situation that appears typical of all the annexin-S100 protein complexes described thus far. However, whereas in the cases of other annexin-S100 complexes the C-terminal extension of the S100 molecule appears indispensable for annexin binding, the annexin VI binding site cannot be restricted to the S100A1 and S100B C-terminal extension. We speculate that the annexin VI site on S100A1/B may only partially overlap to the desmin/GFAP site. In contrast, no effects of annexin V on the ability of S100A1 or S100B to affect the desmin and GFAP assemblies could be documented, although binding of annexin V to S100A1 and S100B could be detected at relatively high Ca2+ concentrations. The present data suggest that annexin VI might regulate S100A1 and S100B activities and vice versa.
Garbuglia
M
M
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Verzini
M
M
Donato
R
R
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017317:Annexin A6 / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D003432:Cross-Linking Reagents; D003893:Desmin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D007382:Intermediate Filaments; D009391:Nephelometry and Turbidimetry / Q000379:methods; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D013050:Spectrometry, Fluorescence
D017304:Annexin A5; D017317:Annexin A6; D002135:Calcium-Binding Proteins; D003432:Cross-Linking Reagents; D003893:Desmin; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C110294:S100A1 protein; D002118:Calcium