Myoclinin 1; Microtubules; modifications post traductionel
Abstract :
[en] Rationale: Juvenile myoclonic epilepsies (JME) are one of the most common forms of genetic generalized epilepsy.
Genetic studies have shown that heterozygous mutations in EFHC1/Myoclonin1 are responsible for 3-22% of JME
cases worldwide. The Myoclonin1 protein contains three DM10 domains of unknown function and an EF-hand domain.
We have previously demonstrated that Myoclonin1 is a microtubule-associated protein involved in cell division and
radial migration during neocortex development. In cells, this protein co-localized with specific structures rich in
microtubules (MTs) such as the centrosome, the poles of the mitotic spindle or the motile cilia but not with cytoplasmic
MTs. This suggests post-translational modifications (PTM) of MTs may be important for the interaction between
Myoclonin1 and MTs
Methods: We co-expressed the different enzymes catalyzing PTM of MTs with Myoclonin1 in U2OS cell line, and then
performed immunocytochemistry and western blot analysis. We next performed pulldown and luciferase
complementation assays to test protein interaction
Results: With one of these enzymes, we observed a strong increase in PTM in the presence of Myoclonin-
1.Interestingly, the effect is observed even when a DM10 domain alone is co-expressed with the enzyme, suggesting
for the first time a role for this domain. This suggests that Myoclonin1 may interact with and modulate the activity of
this enzyme. By using luciferase complementation assay and pull down experiments, we could demonstrate that both
proteins interact.
Conclusions: Our data suggest Myoclonin-1 modulates specific PTM of MTs. This is of prime importance for
microtubule dynamic and notably for neuroblast precursor migration during neocortex development. This could be the
mechanism that explains why pathological forms of myoclonin-1 may affect brain development.
Research center :
Giga-Neurosciences - ULiège
Disciplines :
Neurology
Author, co-author :
Medard, Laurie ; Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique