by Carsten Janke, Institut Curie, Orsay, France
Host: Thomas Surrey
Microtubules are highly versatile cytoskeletal fibres that fulfil essential functions in every eukaryotic cell. Despite this functional diversity, microtubules and their basic building blocks – the tubulin proteins – are highly conserved throughout evolution. One of the key questions in biology is thus how microtubules can adapt to different functions. I will present how a mechanism called the Tubulin Code contributes to the functional diversification of the microtubule cytoskeleton.
Tubulin is expressed from different genes (isotypes) and abundantly posttranslationally modified. While this molecular diversity does in most cases only subtly change the behaviour of the microtubule cytoskeleton at the molecular level, it appears that it has strong impacts at the organism and lifetime scale.
Our lab uses mouse models in which single or multiple tubulin-modifying enzymes are knocked out to determine their physiological functions. We demonstrated that alterations in the tubulin modification glutamylation causes neurodegeneration with defects in axonal cargo transport. Changes in glutamylation can also lead to male infertility and retina degeneration. When we abolished another modification, glycylation, we observed male subfertility in mice with sperm swimming along abnormal trajectories. Our current focus is to determine the molecular mechanisms underlying those physiological functions, which we do in a combination of in-vitro reconstitution and cell-biology experiments.“More