ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating β1 integrin function

• DOI: 10.1242/jcs.00699
• Publication Date: 2003-08-19T00:35:28Z
• Authors: Nobuko Kawaguchi; Christina Sundberg; Marie Kveiborg; Behzad Moghadaszadeh; Meena Asmar; Nikolaj Dietrich; Charles K. Thodeti; Finn C. Nielsen; Peter Möller; Arthur M. Mercurio; Reidar Albrechtsen; Ulla M. Wewer
• Keywords: Vinculin

Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression ADAM12, disintegrin and metalloprotease, dramatically affects morphology preadipocytes, changing them from flattened, fibroblastic appearance to more rounded shape. We showed highest levels ADAM12 mRNA were detected preadipocytes at critical stage when become permissive for adipogenic Furthermore, as assessed by immunostaining, was transiently expressed surface concomitant with reduced activity beta1 integrin. Co-immunoprecipitation studies indicated formation ADAM12/beta1 integrin complexes these preadipocytes. Overexpression 3T3-L1 achieved transient transfection or retroviral transduction led disappearance extensive network actin stress fibers characteristic cells, its reorganization into cortical located beneath membrane. The cells became rounded, exhibited fewer vinculin-positive focal adhesions, adhered less efficiently fibronectin attachment assays. Moreover, ADAM12-expressing prone apoptosis, which could be prevented treating beta1-activating antibodies. A re-organized fibronectin-rich extracellular matrix accompanied changes. addition, readily extracted Triton X-100 overexpressing than control cells. Collectively, results show impairs function integrins and, consequently, alters organization cytoskeleton matrix. These events may necessary early adipocyte