Cell Biology Essay: Using specific examples, describe the structure and function of the accessory proteins which interact with microtubules.
Microtubules are vital structural components of the cytoskeleton in a cell. Their main functions involve the intracellular transport of organelles and vesicles within the cell, and also heavily participate in cellular processes such as mitosis and cytokinesis. They are made up of a- and Β-tubulin dimers that polymerise into protofilaments, and these protofilaments (usually thirteen), arrange into a long, hollow cylinder with a slow growing minus-end and a fast growing plus-end. They are typically anchored at their minus-end in the microtubule organising centre (MTOC) close to the nucleus. Microtubules are known to interact and bind with a growing number of accessory proteins within the cell. There are many different types of accessory proteins, all with differing affects on the assembly, stability and structure of microtubules.
One important group of accessory proteins are known as Stabilizers. They simply serve to stabilize the structure of microtubules by preventing disassembly. This group of proteins are termed MAPs (microtubule-associated proteins), almost all of which bind tightly along the sides of the microtubules, though a rare few are known to interact at the ends of the polymer. MAPs are very commonly found in vertebrate nerve cells and brain glia, where they determine spacing between microtubules and other components. A specific group of MAPs, containing MAP2 and Tau share similar structures. They are rod-shaped, made up of a binding domain, the part that interacts with the microtubule, and a projecting domain. The C-terminal that acts as the tubulin-binding part on the binding domain has three or four tandem repeats that are separated by linkers. These repeats bind to the outer surface of the tubulin monomers along the microtubule polymer. The N-terminal acts as the projecting domain, which contributes to cross-linking and filament bundling. The length of the projecting 'arm' is variable in the different accessory proteins. For example, MAP2 extensions are long which means that when they interact with other microtubules, bundling will be widely spaced. Tau however, has a much shorter extension so forms bundles that are much more closely packed. These differences are evident in the different parts of the nerve cell. MAP2 is highly concentrated in dendrites which cause the wider spacing between microtubules, compare this to axons where tau is more abundant and spacing is closer. The diagram from Alberts et al.  below demonstrates this.
MAPs clearly have a stabilizing effect on microtubules by accelerating nucleation and preventing the occurrence of rapid depolymerisation known as catastrophe. Figures from Pollard and Earnshaw  state that:
'... in the presence of tau, microtubules grow three times faster, shorten in half the time, and have catastrophes only 2% as frequently as pure tubulin microtubules.'
However, the ability of MAPs to stabilize microtubules can be inhibited by phosphorylation from specific protein kinases. These enzymes have a high affinity for the tubulin-binding part of the MAP, causing phosphorylation and thereby inhibiting the binding of the MAP to the microtubule. As a result, the microtubules are destabilized. This method of phosphorylation is important in the regulation of the activity of MAPs.
Another group of accessory proteins have the complete opposite effect of MAPs. They are classed as Destabilizers. They generally function by breaking up the microtubule polymer through inducing the catastrophe state that involves rapid depolymerisation. One example of a destabilizer is the stathmin/Op18 protein. It acts as an important regulator of microtubule dynamics by interacting with the tubulin subunits rather than the polymer itself. Cassimeris  points out that stathmin/Op18's destabilizing activity is due to the combination of both 'catastrophe promotion' and 'sequestering of tubulin dimers', which has recently been discovered via in vitro assays. Stathmin is a small protein, approximately 18 kDa in size consisting of a long a-helix that has a high affinity for tubulin molecules. One stathmin molecule binds to two aΒ-tubulin dimers forming a tight complex. The tubulin dimers can no longer join to the (+)-end of the microtubule. The concentration of free dimers available for binding then decreases, and so subunit addition is blocked. As a result, the rate of polymerisation eventually equals that of GTP hydrolysis and so the GTP cap is lost. At this point, the microtubule enters the rapid shrinking state (catastrophe). Like MAPs, stathmin's activity is controlled by phosphorylation. The cell has specific signals which direct protein kinases to phosphorylate stathmin, inhibiting its effects by weakening the binding to tubulin. More tubulin dimers become available again allowing for assembly. This is particularly important during the cell cycle when cells are required to form the mitotic spindle.