Essential Cell Biology 5th edition

Microtubules
583
nucleus
centrosome
growing
microtubule
microtubule
capping
protein
(A) (B) (C) (D)
unstable
microtubules
stable
microtubules
This remarkable behavior—switching back and forth between polymerization
and depolymerization—is known as dynamic instability. It
allows microtubules to undergo rapid remodeling, and is crucial for their
function. In a normal cell, the centrosome (or other organizing center) is
continually shooting out new microtubules in different directions in an
exploratory fashion, many of which then retract. A microtubule growing
out from the centrosome can,
ECB5
however,
e17.14-17.15
be prevented from disassembling
if its plus end is stabilized by attachment to another molecule or cell structure
so as to prevent its depolymerization. If stabilized by attachment to a
structure in a more distant region of the cell, the microtubule will establish
a relatively stable link between that structure and the centrosome
(Figure 17–15). The centrosome can thus be compared to a fisherman
casting a line: if there is no bite at the end of the line, the line is quickly
withdrawn, and a new cast is made; but, if a fish bites, the line remains in
place, tethering the fish to the fisherman. This simple strategy of random
exploration and selective stabilization enables the centrosome and other
nucleating centers to set up a highly organized system of microtubules in
selected parts of the cell. The same strategy is used to position organelles
relative to one another.
Figure 17–15 Microtubules can be
stabilized by attachment to capping
proteins. A newly formed microtubule will
persist only if both its ends are protected
from depolymerization. In cells, the
minus ends of microtubules are generally
protected by the organizing centers from
which the microtubules grow. The plus ends
are initially free but can be stabilized by
binding to specific capping proteins.
(A) Here, for example, a nonpolarized cell
is depicted with new microtubules growing
from a centrosome in many directions,
before shrinking back randomly. (B) If a
plus end happens to encounter a capping
protein in a specific region of the cell cortex,
that microtubule will be stabilized. (C and D)
Selective stabilization at one end of the cell
will bias the orientation of the microtubule
array, such that an organized system of
microtubules will be set up selectively in
one part of the cell.
Dynamic Instability Is Driven by GTP Hydrolysis
The dynamic instability of microtubules stems from the intrinsic capacity
of tubulin dimers to hydrolyze GTP. This energetically favorable reaction,
which generates GDP and inorganic phosphate, is similar to the hydrolysis
of ATP (see Figure 3−30).
Each free tubulin dimer contains one GTP molecule tightly bound to
β-tubulin, which hydrolyzes the GTP to GDP shortly after the dimer is
added to a growing microtubule. The GDP produced by this hydrolysis
remains tightly bound to the β-tubulin. When polymerization is proceeding
rapidly, tubulin dimers add to the end of the microtubule faster than
the GTP they carry is hydrolyzed. As a result, the end of a rapidly growing
microtubule is composed entirely of GTP-tubulin dimers, which form a
“GTP cap.” GTP-associated dimers bind more strongly to their neighbors
in the microtubule than do dimers that bear GDP, and they pack together
more efficiently. Thus the microtubule will continue to grow (Figure
17–16A).
Because of the randomness of chemical processes, however, it will occasionally
happen that the tubulin dimers at the free end of the microtubule
will hydrolyze their GTP before the next dimers are added, so that the
free ends of protofilaments are now composed of GDP-tubulin. These
GDP-bearing dimers associate less tightly, tipping the balance in favor of
disassembly (Figure 17–16B). Because the rest of the microtubule is composed
of GDP-tubulin, once depolymerization has started, it will tend to
continue; the microtubule starts to shrink rapidly and continuously and
may even disappear.
The GDP-tubulin that is freed as the microtubule depolymerizes joins the
pool of unpolymerized tubulin already in the cytosol. In a typical fibroblast,
for example, about half of the tubulin in the cell is in microtubules,