Tubulins

Tubulins are a family of conserved globular proteins that polymerize to form microtubules, the hollow cylinders of the cytoskeleton. The functional unit is a heterodimer of alpha-tubulin and beta-tubulin. A third class, gamma-tubulin, nucleates microtubule assembly at microtubule organizing centers such as the centrosome, via gamma-tubulin ring complexes. Additional isotypes exist in many species and tissues, providing specialized properties.

Each tubulin binds guanine nucleotides. Alpha-tubulin binds GTP non-exchangeably; beta-tubulin binds GTP and GDP during turnover. Dimerization and GTP hydrolysis on beta-tubulin drive microtubule assembly and disassembly. Microtubules display dynamic instability, with growth and shrinkage regulated by a GTP-tubulin cap at the plus end.

Polymerization begins with nucleation at MTOCs, followed by elongation as dimers add to the growing ends. Minus ends are typically anchored, while plus ends undergo rapid dynamics. Microtubules are regulated by microtubule-associated proteins and are tracks for motor proteins such as kinesins and dyneins that transport cargo and organize intracellular architecture.

Functions include maintaining cell shape, organelle positioning, and chromosome segregation during mitosis. They are essential for forming and operating cilia and flagella, enabling movement of cells and fluids in several tissues.

Drugs that target tubulin affect cell division and are used in cancer therapy. Microtubule-stabilizing agents like paclitaxel and docetaxel, and destabilizing agents such as vinca alkaloids, disrupt microtubule dynamics and arrest mitosis. Mutations in tubulin genes can cause tubulinopathies with neurological and developmental disorders.

Humans express multiple tubulin isotypes encoded by separate genes, including alpha-, beta-, and gamma-tubulin families. These isotypes show tissue-specific expression and contribute to functional diversity of microtubules in neurons, cilia, and other cells.