CLIP-170 (red and blue) helps rescue shrinking microtubules (green).

Microtubules grow persistently from the centrosome to the cell margin, and then enter a state of dynamic instability, repeatedly growing and shrinking over short distances to probe the margin of the cell. This process is thought to be critical for rapid sensing of cell shape changes. On page 589, Komarova et al. demonstrate that the cytoplasmic linker proteins (CLIPs) are important and highly specific regulators of dynamic instability. The work helps explain why microtubules normally probe only the cell margin, rather than growing and shrinking over greater distances.The authors found that expression of a truncated form of the CLIP protein CLIP-170 acts in a dominant–negative fashion in cultured mammalian cells, knocking endogenous CLIPs off their normal perches on the plus ends of microtubules. Though this has no effect on the rate of microtubule growth or shortening, it significantly reduces the frequency with which shrinking microtubules are rescued, or switched from shortening to growth. When rescue is inhibited, the microtubules still grow persistently from the centrosome to the cell margin; but once shortening begins, the microtubules shrink persistently back toward the centrosome, probing the entire cytoplasm. The results suggest that CLIPs normally bind to tubulin dimers, which then bind to shortening microtubules to convert them to the growth phase. ▪