Unstable microtubules create dense-boned mice, according to Gil-Henn et al. The authors show that bone-eating osteoclasts go hungry without the stabilizing activity of the Pyk2 tyrosine kinase.
In osteoclasts, Pyk2 resides mainly in podosomes, actin-rich structures that help attach osteoclasts to the underlying bone. Organized in a belt-like structure at the cell periphery, podosomes create a sealed zone between the cell and the bone. Beneath this zone, osteoclasts lower the pH and secrete enzymes that degrade bone to counter its production by osteoblasts.
Podosome belts and sealing zones form by the fusion of small actin rings at the cell periphery. This fusion appears to fail in osteoclasts from mice lacking Pyk2 due to instability of their microtubule network, causing faulty bone destruction and thick-boned mice.
Microtubule instability was accompanied by a reduction in the acetylation of microtubules in osteoclasts lacking Pyk2. Additionally, Rho activity was...
