Microtubule Cytoskeletal Proteins as Targets for Covalent Interconverting Enzymes

Abstract

Microtubules are highly organized, supramolecular arrays of tubulin protomers that play central structure- and motility-linked roles in eukaryotes. Many studies have demonstrated that interphase cells display a characteristic lacelike network of microtubules that originate at centriolar regions, span the cytoplasm, and terminate at the cell's margin or outer membrane. In addition to providing the molecular framework for cell shape and chromosomal movement, microtubules are intimately involved in ciliary and flagellar processes, neuronal axoplasmic transport, and even sensory transduction events. The formation of microtubules and cytoskeletal networks is a complex process involving the interaction of many components. The in vitro self-assembly process is conceptualized by the Oosawa condensation equilibrium model that involves sequential, but not necessarily time-resolved, reactions known as nucleation, elongation, protomer–polymer equilibration, and polymer length redistribution. The ATP-dependent insertion of tyrosine into tubulin as a posttranscriptional event was first observed in brain extracts, but the identification of the protein as tubulin came several years later. Another type of interconverting enzyme involving microtubule proteins is the calcium-activated neutral protease found in synaptosomal extracts and whole brain extracts.