ROLE OF MICROTUBULE-ASSOCIATED PROTEINS IN THE CONTROL OF MICROTUBULEASSEMBLY

In eukaryotic cells, microtubules, actin, and intermediate filaments i nteract to form the cytoskeletal network involved in determination of cell architecture, intracellular transport, modulation of surface rece ptors, mitosis, cell motility, and differentiation. Cytoskeletal organ ization and dynamics depend on protein self-associations and interacti ons with regulatory elements such as microtubule-associated proteins ( MAPs). The MAP family includes large proteins like MAP-1A, MAP-1B, MAP -1C, MAP-2, and MAP-4 and smaller components like tau and MAP-2C. This review focuses on relevant aspects of MAP function, with emphasis on their roles in modulating cytoskeletal interactions. In this context, MAP expression mechanisms and posttranslational modifications are also discussed. Microtubule-associated proteins have a rather widespread d istribution among cells, but certain MAPs have been identified in spec ific cell types. Within single neurons, MAP-2 is dendritic while tau i s preferentially an axonal protein. Their expression is developmentall y regulated. Even though MAPs share a capacity to interact with the CO OH-terminal tubulin domain, stabilize microtubules, and link them with other cytoskeletal polymers, they exhibit structural differences. How ever, MAP-2, MAP-4, and tau have common repetitive microtubule-binding motifs. Microtubule-associated proteins not only control cytoskeletal integrity, but they also appear to interact with highly structural el ements of cells. Molecular biological approaches permitted localizatio n of new MAPs in cultured mammalian cells and invertebrate organisms a nd other microtubule-interacting proteins that exhibit transient inter actions with microtubules. The structural/functional aspects of severa l new MAP-like proteins in centrosomes and the mitotic spindle, functi onally implicated in cell cycle events, are also analyzed.