Penn Medicine

Yale Goldman, M.D., Ph.D.

Dixit R, Barnett B, Lazarus JE, Tokito M, Goldman YE, Holzbaur EL.

Microtubule Plus-End Tracking by CLIP-170 Requires EB1.

Proc. Nat. Acad. Sci. 106:492-497. 2009.

Plus-end tracking proteins ('+TIPs') are a special class of microtubule-associated proteins that associate with the growing ends of microtubules {1}. Because many of these proteins interact with tubulin and with each other, it has been difficult to determine the precise mechanisms of how they localize to the growing microtubule end. Two opposing models have been: on one hand, the 'copolymerization' model, in which +TIPs bound to tubulin dimer incorporate into the microtubule lattice as a single molecular entity, with the +TIPs dissociating at some point afterwards, and, on the other hand, the 'end-recognition' model, in which +TIPs bind to the growing lattice by recognizing structural features (i.e. tubulin subunit conformations) that are unique to the tip of the lattice. This study, together with other recent in vivo work {2}, comes down firmly on the side of the latter model. Using purified proteins, the authors show that EB1, probably the most conserved of all +TIPs, binds autonomously to the growing microtubule end and also turns over very quickly in repeated cycles of dissociation and rebinding. By contrast, the 'founder' member of the +TIP proteins, CLIP-170, shows similar tracking behavior and turnover in the presence of EB1, but in the absence of EB1, CLIP-170 binds more uniformly along the entire microtubule lattice, without any preference for the growing ends. This is a 'textbook' study, with remarkably clear results, and similar results have also been obtained independently by another lab {3} (see evaluation). It is also interesting that these results differ, in a biologically interesting way, from those obtained in an earlier study using purified fission yeast proteins {4}. The nature of the differences suggests that the mechanisms involved in +TIP behavior are likely not 'fundamentally' different in different biological systems but rather that subtle modifications -- variations on a core mechanism -- are likely to be responsible for what might appear to be significant differences in vivo.

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