Myoclonin1 modulates the post-translational modification of microtubules
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1
Liège University, GIGA Neurosciences, Belgium
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2
Maastricht University, Netherlands
Juvenile myoclonic epilepsy is one of the most common forms of generalized genetic epilepsy. Genetic studies have shown that heterozygous mutations in Myoclonin1 are responsible for 3-9% of clinical cases worldwide. This 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.
We have co-express the different enzymes catalyzing PTM of MTs with Myoclonin1 in U2OS cell line. With one of these enzymes, we observed a strong increase in PTM in the presence of Myoclonin-1. 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 it is indeed the case. 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.
In conclusion 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 affect brain development.
Acknowledgements
This work was supported by the FRS-FNRS (PDR n° T.0009.13), the Leon Frederique Fondation (to LM) and the Fonds Speciaux of the University of Liège (FSRC-13/67).
LM is fellow of the Fonds pour la Recherche dans l'Industrie et l'Agriculture (FRIA). BL is Research Associate at the FRS-FNRS.
Keywords:
JME,
Myoclonin1,
Post-translational modifications (PTMs),
Epilepsy,
Microtubules
Conference:
11th National Congress of the Belgian Society for Neuroscience, Mons, Belgium, 22 May - 22 May, 2015.
Presentation Type:
Poster presentation
Topic:
Neuroscience
Citation:
MEDARD
L,
GODIN
J,
COUMANS
B,
LAKAYE
B and
De NIJS
L
(2015). Myoclonin1 modulates the post-translational modification of microtubules.
Front. Neurosci.
Conference Abstract:
11th National Congress of the Belgian Society for Neuroscience.
doi: 10.3389/conf.fnins.2015.89.00015
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Received:
05 May 2015;
Published Online:
05 May 2015.
*
Correspondence:
Miss. Laurie MEDARD, Liège University, GIGA Neurosciences, LIEGE, 4000, Belgium, l.medard@ulg.ac.be