nontubulin

Nontubulin is a term used to describe all cellular components that are not tubulin, particularly in discussions of the microtubule cytoskeleton. Microtubules are dynamic polymers built from α- and β-tubulin; nontubulin proteins regulate their assembly, stability, and interactions with other cellular structures.

Major groups of nontubulin components include microtubule-associated proteins (MAPs), where proteins such as tau, MAP2, and MAP4 bind along microtubules and influence stability and spacing. End-binding proteins (+TIPs) like EB1 and CLIP-170 regulate microtubule plus-end dynamics. Motor proteins such as kinesins and dyneins are not tubulin themselves but drive transport along microtubules. Microtubule-severing enzymes, including katanin, spastin, and fidgetin, remodel microtubule networks by cutting filaments. Regulatory factors such as stathmin/Op18 influence polymerization by sequestering tubulin dimers. In addition, tubulin biogenesis involves non-tubulin cofactors and chaperones (e.g., TBCA–TBCD, prefoldin, CCT) that assist tubulin folding and assembly. Gamma-tubulin ring complex, though containing gamma-tubulin, comprises multiple non-tubulin subunits that nucleate microtubule formation.

Function: Nontubulin proteins control microtubule nucleation, growth, shrinkage, and catastrophe; mediate interactions with organelles, membranes, and cytoskeletal crosslinkers; and coordinate spindle assembly and chromosome segregation during mitosis.

Clinical and research relevance: Alterations in nontubulin components are linked to neurodegenerative diseases (tauopathies), hereditary spastic paraplegia, and various cancers. They are targets for studies aimed at understanding cell polarity, intracellular transport, and cell division.