Tubulin modifications and cytoskeleton dynamics

• Applicant: Dr. Marco van Ham, since 9/2010
• Subject Area: Cell Biology
• Term: from 2006 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 14023866

Microtubules, which are centrally involved in cell division, cell motility, cell morphogenesis and intracellular motile events, are built of aß-tubulin dimers. Both subunits can be subject of C-terminal post-translational modifications, of which one, the detyrosination of a-tubulin, is part of the so called tubulin tyrosination cycle and involves the enzymatic cyclic removal of the C-terminal tyrosine from a-tubulin while incorporated into microtubules and re-addition of this amino acid to soluble aß-tubulin dimers after microtubule depolymerisation. The tubulintyrosine- ligase (TTL), which catalyses the latter step, has been identified (Arce et al., 1975) and characterised, whereas the tubulin specific carboxypeptidase (TCP) has remained elusive. The physiological role of this tubulin tyrosination cycle is still ill defined. However, we have recently gained first insights into the physiological relevance of this tubulin modification by generating and analysing TTL-deficient mice, which died perinatally due to severe neuronal malformations (Erck et al., 2005). For further in depth analysis of this modification cycle we will (1) generate conditional TTL knockout mice, (2) study the consequences of TTL deficiency in various tissues and pre- and post-mitotic cells and (3) enrich the TCP-activity with the ultimate goal to identify the responsible protein or protein complex.

• DFG Programme: Research Units
• Subproject of: FOR 629: Molecular Mechanisms of Cell Motility
• Ehemaliger Antragsteller: Professor Dr. Jürgen Wehland, until 9/2010 (†)