Wen-Cheng Xiong and Xu Feng

Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294

FIGURES

Figure 1. Mechanism of Osteoclastic Bone Resorption. Several structural features of osteoclasts are important for bone resorption. To resorb bone, osteoclasts tightly attach onto bone matrix through the "sealing zone", which seals the resorption site from its surroundings. The second feature is the formation of ruffled membrane that is rich in proton pumps (H-ATPase). Proton pumps transport protons into the resorption site to dissolve the inorganic bone matrix (hydroxyapatite). In addition, the ruffled membrane also transport proteolytic enzymes that degrade the organic bone matrix (collagen I). The ruffled membrane is formed by fusion of intracellular acidic vesicles via microtubes. Degraded products are removed by transcytosis.

Figure 2. Role of PYK2 in Integrin avb3-mediated Intracellular Siganling in Osteoclasts. In response to integrin avb3 activation, PYK2 is recruited to the podosomes through direct interactions with the b3 integrin cytoplasmic tails. In the integrin avb3-induced signaling complex, PYK2 interacts with paxillin and Cas. However, the functional roles of these interactions have not been clearly revealed. In addition, integrin avb3 activation also induces PYK2 phosphorylation by c-Src and/or a Ca2+-dependent pathway. Phosphorylated PYK2 interacts with other signaling molecules such as c-Src to form signaling complex together with c-Cbl, which was proposed to play a role in osteoclast function. But, the role of this complex in osteoclast function has not been confirmed. Most significantly, recent studies indicate that PYK2 interacts and phosphorylates gelsolin to mediate actin ring formation.