Scientists unravel the mystery of the tubulin code

NIH | MAY 27, 2015

Cellular structures called microtubules are tagged with a variety of chemical markers that can influence cell functions. The pattern of these markers makes up the “tubulin code” and scientists have uncovered the mechanism behind one of the main writers of this code, tubulin tyrosine ligase-7 (TTLL7).

TTLL7 is a protein that adds glutamate tags onto microtubules. There are nine proteins that make up the TTLL family, but TTLL7 is the most abundant in the brain and one of the main tubulin code writers.

The findings define how TTLL7 interacts with microtubules and how members of the TTLL family use common strategies to mark microtubules with glutamate tags.

Microtubules are cylindrical structures that provide shape to cells and act as conveyor belts, ferrying molecular cargo throughout cells. They are marked on their outside surface with a variety of chemical groups. These markers impact a cell’s activity by changing the stability of microtubules, thus affecting cell shape, or by repositioning molecular cargo traveling on the microtubules.

The most common microtubule marker in the brain is glutamate. The addition of glutamate markers to microtubules plays important roles in brain development and brain cell repair following injury. One of the signatures of damaged cells in cancer or blunt trauma is a change in the pattern of these microtubule markers. Mutations in TTLL genes have been linked with several neurodegenerative disorders.

This research may lead to the development of small molecules that can regulate activity of TTLL proteins, which may have implications for disorders linked to mutations in TTLL genes.

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