Rac-GTPase, osteoclast cytoskeleton and bone resorption》.pdf

EJca European Journal of Cell Biology 78, 249-255 (1999, April) . © Urban Fischer Verlag· Jena 249 http://www.urbanfischer.de/iou rna lsieicb Rac-GTPase, osteoclast cytoskeleton and bone resorption l Sieiman Razzouk, Michele Lieberherr, Giulia Coumot ) CNRS-UPR 1524, INRA-LNSA-Biit 221, Jouy en Josas/France Received November 5, 1998 Received in revised version December 28, 1998 Accepted January 20, 1999 Rac-GTPases - osteoclast - cytoskeleton - bone resorption Introduction The members of the Rho-GTPase subfamily, Rac1 and Rac2, are inti- mately involved in the organization of the cytoskeleton, and the p21- Osteoclasts must adhere to the bone surface before they can activated kinases or PAKs are targets of these proteins. Rac1 and Rac2 begin to resorb it. Adhesion is mediated by integrins, receptor are also essential components of NADPH oxidase, the enzyme molecules that interact with extracellular matrix proteins. responsible for generating free radicals. The cytoskeleton modulates The main integrin in osteoclasts is integrin av~3, the vitronec- the adhesion of osteoclasts to bone and its subsequent resorption. tin receptor [3], that binds to a specific tripeptide sequence These cells contain NADPH diaphorase activity, and free radicals (RGD: Arg-Gly-Asp) and acts as a signaling molecule that influence bone resorption. The influence of Rac1, Rac2 and PAKI on transduces informations from the matrix into the cells [19]. the cytoskeleton, resorbing activity and NADPH diaphorase activity The intracytoplasmic pathways involve tyr