New TIPs for successfully growing microtubules

D ynamic microtubules grow and shrink at their plus ends, and the balance between these two processes is regulated by a host of plus end– tracking proteins (+TIPs). van der Vaart et al. (1) and Li et al. (2) describe two new +TIPs that boost microtubule dynamics in mammalian and Drosophila cells. The EB1 family of +TIPs are the master regulators of microtubule plus ends (3). " They can autonomously bind to the growing tips of microtubules, " explains Gohta Goshima from Nagoya University in Japan. " They recruit many other +TIPs, but none of these other proteins can accumulate without EB1. " Anna Akhmanova, from the Erasmus Medical Center and Utrecht University in the Netherlands, and Michel Steinmetz, from the Paul Scherrer Institute in Swit-zerland, used a biochemical pull-down approach to look for additional EB1 binding partners in mammalian cells (1). They identifi ed a strong interaction between EB1's C terminus and a largely uncharac-terized protein called SLAIN2. SLAIN2 localized to microtubule plus ends in cells, where it not only bound EB1 but several other +TIPs as well, including members of the CLASP and CLIP families. Akhmanova says that this network of interactions helps +TIPs stay associated with growing microtubule ends. " All the +TIPs compete with each other at plus ends, so it's good to have several different binding sites. " van der Vaart et al. were particularly interested in SLAIN2's interaction with ch-TOG, the mammalian homologue of the microtubule polymerase XMAP215. " ch-TOG is the only protein known to strongly accelerate microtubule growth, " says Akhmanova. When the interaction between SLAIN2 and ch-TOG was disrupted—either by depleting SLAIN2 or by expressing a dominant negative version of the protein— ch-TOG was no longer recruited to micro-tubule plus ends. " Microtubules then have diffi culty growing, " Akhmanova says. " They only polymerize in very short bursts. " This was somewhat surprising because, in vitro, XMAP215 is capable of binding and polymerizing microtubules by itself (4). " We think that SLAIN2 is needed in vivo because microtubule plus ends are a competitive environment, " Akhmanova explains. " SLAIN2 is a linker that positions and concentrates ch-TOG at the tips. " This activity is no longer required in mitosis when, the researchers found, SLAIN2 is highly phos-phorylated, which blocks its interactions with EB1 and ch-TOG. " Microtubules behave differently during mitosis, so a lot of +TIP interactions are fi ne-tuned, …