Ttll7, short for Tubulin tyrosine ligase-like 7, is a key enzyme involved in tubulin polyglutamylation, a post-translational modification of microtubules. Microtubules form a cytoskeletal framework influencing cell shape, and polyglutamylation is crucial for neuronal functions. Ttll7 specifically modulates the activities of microtubule-interacting proteins, is involved in regulating glutamate concentration in the brain, and is important for the growth of MAP2-positive neurites [1].

In gene knockout studies, Ttll7 knockout mice showed abnormal behaviors, and MALDI-IMS analyses of their brains indicated an increase in glutamate, suggesting that Ttll7-mediated tubulin polyglutamylation acts as a glutamate pool in neurons [1]. In primary cultures of superior cervical ganglion neurons, knockdown of Ttll7 led to a loss of polyglutamylated beta-tubulin, and in PC12 cells, siRNA-mediated knockdown of Ttll7 repressed nerve growth factor-stimulated MAP2-positive neurite growth [2].

In conclusion, Ttll7 plays essential roles in neuronal functions such as neurite growth and glutamate regulation. Gene knockout mouse models have been instrumental in revealing these functions, providing insights into the potential mechanisms underlying neurological disorders associated with disrupted glutamate metabolism and neurite development [1,2].

References:

1. Ping, Yashuang, Ohata, Kenji, Kikushima, Kenji, Konishi, Yoshiyuki, Setou, Mitsutoshi. 2023. Tubulin Polyglutamylation by TTLL1 and TTLL7 Regulate Glutamate Concentration in the Mice Brain. In Biomolecules, 13, . doi:10.3390/biom13050784. https://pubmed.ncbi.nlm.nih.gov/37238654/

2. Ikegami, Koji, Mukai, Masahiro, Tsuchida, Jun-ichi, Macgregor, Grant R, Setou, Mitsutoshi. 2006. TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2-positive neurites. In The Journal of biological chemistry, 281, 30707-16. doi:. https://pubmed.ncbi.nlm.nih.gov/16901895/