Binding sites (orange) for CLIP-170 are abundant at microtubule plus ends (top) but disappear as the filament grows (bottom).

Microtubule tips are a hotbed of weak binding sites, say Dragestein et al. The authors suggest a new model to describe the behavior of microtubule plus end–binding proteins.

The plus end of a microtubule—its growing end—attracts a variety of binding proteins, including EB1 and CLIP-170, which are thought to influence microtubule dynamics. Viewed on a growing microtubule, fluorescently labeled CLIP-170 appears as a comet: a bright dot at the tip trailed by a progressively fainter tail.

Current explanations for the comet postulate that CLIP-170 hops onto the tip, perhaps together with tubulin, hangs on for a couple seconds as the microtubule grows, and then falls off behind the tip. But the new work reveals that CLIP-170 hops on and off much faster.

Measurements of exchange rates using fast FRAP revealed that CLIP-170 only held on for ∼0.3 seconds before hopping off a microtubule. Measurements were limited by the speed with which CLIP-170 can diffuse to the tip, so true exchange rates might be even faster. CLIP-170 was also equally capable of hopping on at spots that were further back than just the very tip of the plus end, in contrast to the proposals of previous models.

To explain the fluorescent comet, the group now proposes that binding sites for CLIP-170 are more abundant at the microtubule tip (the head of the comet) than further back (the tail). Using fluorescence correlation spectroscopy, they calculated that ∼100 relatively weak binding sites for CLIP-170 were found at the tip. Why binding sites disappear at a distance from the tip is not clear. Perhaps tubulin undergoes structural changes as it is incorporated into the filament.

Exchange rates for EB1 were similar to those of CLIP-170, suggesting that plus end–binding proteins are generally transient binders. The authors wonder whether quick changes in the structure at plus ends might relay information to other cellular components. They are now aiming to do single-molecule imaging on microtubule plus ends inside cells.


Dragestein, K.A., et al.
J. Cell Biol.