.jpg)
Microtubules (MTs) are key elements of eukaryotic cells and play a vital role in cell division, morphogenesis, organization and motility. In mitotic cells, MTs are centrally involved in the mechanic and control of cell division and there is strong evidence that abnormalities of elements of the mitotic machinery are major factors favoring tumor progression. MTs are also important for cytoplasmic organization and organelle trafficking in interphasic cells, especially in neurons, whose asymmetry is extreme.
Our team is investigating microtubule effectors that affect MT dynamics or tubulin structure. We characterize such effectors at the molecular and cellular levels, we test their functional importance in animal models and we assess their involvement in human pathologies.
Our research program will focus on:
• Study of the role of MT stability effectors in neuronal function and plasticity events. We have shown that STOP proteins are crucially involved in synaptic function. STOP-deficient mice display synaptic and behavioural defects related to schizophrenia. We intend to use STOP deficient mice as a model system to investigate the origin and treatment of schizophrenia. We wish to elucidate the molecular role of STOP/ STOP-related proteins in synaptic modulation by studying the relationship between microtubule dynamic, vesicular trafficking and plasticity events.
• Study of the role of the C-terminal amino acid of the tubulin dimers in MTs functions during mitosis and cell differentiation. The C-terminal tyrosine residue of alpha tubulin is cyclically removed from the peptide chain by an ill-defined carboxypeptidase (TCP) and re-added to the chain by a tubulin-tyrosine-ligase (TTL). Observations obtained from examination of TTL null cells and animals indicate that the integrity of the C-terminus of tubulin is required for proper interactions between MTs plus end proteins and the cell cortex. We will extend the characterization of TTL null phenotypes in cells, tissues and animals. We will try to identify and to characterize the tubulin carboxypetidase (TCP).
• Study of basic mechanisms involved in MTs formation from tubulin dimers (nucleation, elongation and disassembly). Then, we will try to determine how cells use these intrinsic properties during different physiological states (quiescence, mitosis or terminal differentiation).
Bienvenue
 Director |
||
|
||
| Members |
||
 |
||
| Introduction |
||
| Research interests |
||
 STOP proteinsTubulin tyrosination cycleMTs + ends complexes characterizationMicrotubule dynamics |
||
| Key words |
||
|
Microtubules, cytoskeleton, dynamic, tubulin, microtubule associated proteins, motors, centrosomes, post-traductionnal modifications, cellular proliferation, mitose, cancer, agents thérapeutiques, morphogenèse cellular morphogenesis, neurone, maladie neurologique et psychiatrique, development, transgenesis, molecular biology, optical microscopy, microinjection, electronic microscopy, biochemistry.
|