While very few microtubule minus-end-binding proteins have been characterized, a large subset of MAPs has been identified that are enriched at microtubule plus ends. A particularly ubiquitous example is XMAP215, which has close homologs in organisms that range from yeast to humans. XMAP215 binds free tubulin subunits and delivers them to the plus end, thereby promoting microtubule polymerization and simultaneously counteracting catastrophe factor activity (see Figure 16–52). The phosphorylation of XMAP215 during mitosis inhibits
GTP cap on plus end of microtubule
Figure 16–51 Organization of microtubule bundles by MAPs. (A) MAP2 binds along the microtubule lattice at one of its ends and extends a long projecting arm with a second microtubule-binding domain at the other end. (B) Tau possesses a shorter microtubule cross-linking domain.
Electron micrograph showing a cross section through a microtubule bundle in a cell overexpressing MAP2. The regular spacing of the microtubules (MTs) in this bundle results from the constant length of the projecting arms of the MAP2.
Similar cross section through a microtubule bundle in a cell overexpressing tau. Here the microtubules are spaced more closely together than they are in (C) because of tau’s relatively short projecting arm. (C and D, courtesy of J. Chen et al., Nature 360:674–677, 1992. With permission from Macmillan Publishers Ltd.)
Figure 16–52 The effects of proteins that bind to microtubule ends. The transition between microtubule growth and shrinkage is controlled in cells by a variety of proteins. Catastrophe factors such as kinesin-13, a member of the kinesin motor protein superfamily, bind to microtubule ends and pry them apart, thereby promoting depolymerization. On the other hand, a MAP such as XMAP215 stabilizes the end of a growing microtubule (XMAP stands for Xenopus microtubuleassociated protein, and the number refers to its molecular mass in kilodaltons). XMAP215 binds tubulin dimers and delivers them to the microtubule plus end, thereby increasing the microtubule growth rate and suppressing catastrophes.
its activity and shifts the balance of its competition with catastrophe factors. This shift results in a tenfold increase in the dynamic instability of microtubules during mitosis, a transition that is critical for the efficient construction of the mitotic spindle (discussed in Chapter 17).
In many cells, the minus ends of microtubules are stabilized by association with a capping protein or the centrosome, or else they serve as microtubule depolymerization sites. The plus ends, in contrast, efficiently explore and probe the entire cell space. Microtubule-associated proteins called plus-end tracking proteins (+TIPs) accumulate at these active ends and appear to rocket around the cell as passengers at the ends of rapidly growing microtubules, dissociating from the ends when the microtubules begin to shrink (Figure 16–53).