PT  - JOURNAL ARTICLE
AU  - Amelia L Parker
AU  - Wee Siang Teo
AU  - Elvis Pandzic
AU  - Juan Jesus Vicente
AU  - Joshua A McCarroll
AU  - Linda Wordeman
AU  - Maria Kavallaris
TI  - β-Tubulin carboxy-terminal tails exhibit isotype-specific effects on microtubule dynamics in human gene-edited cells
AID  - 10.26508/lsa.201800059
DP  - 2018 May 01
TA  - Life Science Alliance
PG  - e201800059
VI  - 1
IP  - 2
4099  - https://www.life-science-alliance.org/content/1/2/e201800059.short
4100  - https://www.life-science-alliance.org/content/1/2/e201800059.full
SO  - Life Sci. Alliance2018 May 01; 1
AB  - Microtubules are highly dynamic structures that play an integral role in fundamental cellular functions. Different α- and β-tubulin isotypes are thought to confer unique dynamic properties to microtubules. The tubulin isotypes have highly conserved structures, differing mainly in their carboxy-terminal (C-terminal) tail sequences. However, little is known about the importance of the C-terminal tail in regulating and coordinating microtubule dynamics. We developed syngeneic human cell models using gene editing to precisely modify the β-tubulin C-terminal tail region while preserving the endogenous microtubule network. Fluorescent microscopy of live cells, coupled with advanced image analysis, revealed that the β-tubulin C-terminal tails differentially coordinate the collective and individual dynamic behavior of microtubules by affecting microtubule growth rates and explorative microtubule assembly in an isotype-specific manner. Furthermore, βI- and βIII-tubulin C-terminal tails differentially regulate the sensitivity of microtubules to tubulin-binding agents and the microtubule depolymerizing protein mitotic centromere-associated kinesin. The sequence of the β-tubulin tail encodes regulatory information that instructs and coordinates microtubule dynamics, thereby fine-tuning microtubule dynamics to support cellular functions.