Microtubule-Associated Proteins

Abstract

Microtubules are formed by polymerization of α- and β-tubulin. They are intrinsically in a dynamic turnover state, subject to treadmilling and dynamic instability. Microtubule-associated proteins (MAPs) are a heterogeneous group of proteins that have microtubule-binding domains. MAPs are abundantly expressed in the brain, and historically MAPs (e.g., MAP1, MAP2, and tau) derived from the brain have been studied extensively. MAP4 is ubiquitously expressed. These classical MAPs are filamentous proteins of various lengths, ranging from 50 to 185 nm. They have a microtubule-binding domain and a projection domain that extends as a filamentous structure. MAPs stabilize microtubules by binding along the side of microtubules. In addition, by extending the projection domain from the microtubule surface, MAPs can produce microtubule bundles of various densities. Tau and MAP2C predominantly expressed in the axon produce microtubule bundles of ~20 nm spacing between microtubules. MAP2 predominantly expressed in the dendrite produces microtubule bundles with ~65 nm spacing. The microtubule bundles produced by tau/MAP2C and MAP2 resemble microtubule domains in axons and dendrites, respectively. These microtubule bundles are extended from the cell as axon- or dendrite-like processes. Therefore, MAPs serve as determinants of microtubule organization within the cell, particularly in neurons. There are also newly identified MAPs, some of which destabilize microtubules. Binding of MAPs to microtubules is regulated by phosphorylation. In some neurodegenerative diseases including Alzheimer׳s disease, hyperphosphorylated tau precipitates as filaments on its own and may be one of the important factors to determine the progress of the disease.