Regulation of microtubule motors by tubulin isotypes and post-translational modifications

Minhajuddin Sirajuddin, Luke M. Rice, Ronald D. Vale

Research output: Contribution to journalArticlepeer-review

382 Scopus citations


The 'tubulin-code' hypothesis proposes that different tubulin genes or post-translational modifications (PTMs), which mainly confer variation in the carboxy-terminal tail (CTT), result in unique interactions with microtubule-associated proteins for specific cellular functions. However, the inability to isolate distinct and homogeneous tubulin 1species has hindered biochemical testing of this hypothesis. Here, we have engineered 25 α /β-tubulin heterodimers with distinct CTTs and PTMs and tested their interactions with four different molecular motors using single-molecule assays. Our results show that tubulin isotypes and PTMs can govern motor velocity, processivity and microtubule depolymerization rates, with substantial changes conferred by even single amino acid variation. Revealing the importance and specificity of PTMs, we show that kinesin-1 motility on neuronal β-tubulin (TUBB3) is increased by polyglutamylation and that robust kinesin-2 motility requires detyrosination of α-tubulin. Our results also show that different molecular motors recognize distinctive tubulin 'signatures', which supports the premise of the tubulin-code hypothesis.

Original languageEnglish (US)
Pages (from-to)335-344
Number of pages10
JournalNature cell biology
Issue number4
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Cell Biology


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