
TTLL10酵素は、既存のモノグリシル化チューブリンに対してのみ高い親和性を示し、ポリグリシル化鎖を伸長する。一方で、ポリグリシル化は逆にTTLL10の微小管への結合を阻害する。また、先行するグルタミル化はTTLL10の微小管結合を促進する。これにより、微小管上の修飾パターンが制御される。


coremsg

Microtubules in cells have complex and developmentally stereotyped posttranslational modifications that support diverse processes such as cell division, ciliary growth and axonal specification. Glycylation, the addition of glycines, singly (monoglycylation) or in chains (polyglycylation), is primarily found on axonemal microtubules where it functions in cilia maintenance and motility. It is catalyzed by three enzymes in the tubulin tyrosine ligase- like family, TTLL3, 8 and 10. We show that TTLL8 monoglycylates both α- and β-tubulin, unlike TTLL3 which prefers β-tubulin. Microscopy and mass spectrometry show that TTLL10 requires monoglycylation for high affinity microtubule binding and elongates polyglycine chains only from pre-existing glycine branches. Surprisingly, tubulin polyglycylation inhibits TTLL10 recruitment to microtubules proportional with the number of posttranslationally added glycines, suggesting an autonomous mechanism for polyglycine chain length control. In contrast, tubulin glutamylation, which developmentally precedes polyglycylation in cilia, increases TTLL10 recruitment to microtubules, suggesting a mechanism for sequential deposition of tubulin modifications on axonemes. Our work sheds light on how the tubulin code is written by establishing the substrate preference and regulation of TTLL glycylases, and provides a minimal system for generating differentially glycylated microtubules for in vitro analyses of the tubulin code.

### Competing Interest Statement

The authors have declared no competing interest.

The TTLL10 polyglycylase is stimulated by tubulin glutamylation and inhibited by polyglycylation

微小管のポリグリシル化を触媒するttll10酵素は-チューブリンのグルタミル化によって活性化され-ポリグリシル化によって阻害される


微小管のポリグリシル化を触媒するTTLL10酵素は、チューブリンのグルタミル化によって活性化され、ポリグリシル化によって阻害される
