the architecture of the adhesive apparatus of cultured osteoclasts from podosome formation to sealing zone assembly的体系结构从podosome培养破骨细胞形成的胶装置密封区组装.pdfVIP

The Architecture of the Adhesive Apparatus of Cultured Osteoclasts: From Podosome Formation to Sealing Zone Assembly 1,2 2 3 4 4 1 2 Chen Luxenburg , Dafna Geblinger , Eugenia Klein , Karen Anderson , Dorit Hanein , Benny Geiger , Lia Addadi * 1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel, 2 Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel, 3 Chemical Research Support Unit, Weizmann Institute of Science, Rehovot, Israel, 4 Infectious Diseases and Cell Adhesion Programs, The Burnham Institute for Medical Research, La Jolla, California, United States of America Background. Osteoclasts are bone-degrading cells, which play a central role in physiological bone remodeling. Unbalanced osteoclast activity is largely responsible for pathological conditions such as osteoporosis. Osteoclasts develop specialized adhesion structures, the so-called podosomes, which subsequently undergo dramatic reorganization into sealing zones. These ring-like adhesion structures, which delimit the resorption site, effectively seal the cell to the substrate forming a diffusion barrier. The structural integrity of the sealing zone is essential for the cell ability to degrade bone, yet its structural organization is poorly understood. Principal Findings. Combining high-resolution scanning electron microscopy with fluorescence microscopy performed on the same sample, we mapped the molecular architecture of the osteoclast resorptive apparatus from individual podosomes to the sealing zone, at an unprecedented resolution. Podosomes are composed of an actin-bundle core, flanked by a ring containing adhesion proteins connected to the core via dome-like radial actin fibers. The sealing zone