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Interview with E Gomes

Edgar Gomes
Edgar Gomes is head of the team " Cytoskeleton architecture and cell polarization ", UMRS787-Myology Group directed by David Sassoon. He has recently co-authored an article in Science* in which a new protein structure involved in nuclear movements during fibroblast polarization is described.
 
What is the importance of this study?
We have identified a new structure consisting of several proteins on the nucleus of the cell called TAN line (transmembrane actin-associated nuclear Lines). TAN is composed of actin filaments and two proteins embedded in the double membrane of the nucleus, which are linked together: Sun2 in the inner membrane and nesprin2G in the outer membrane. They form a bridge between the nucleoskeleton (at the level of the lamins) and the cytoskeleton.
By using in vivo fluorescence microscopy, we were able to examine the localization and behaviour of these three proteins during the movement of fibroblasts nuclei in culture. We observed an array of actin filaments in parallel lines, which, through connections with the nucleus, allows nuclear movement. We also observed structural similarities between the TAN lines and the dystrophin complex: actin filaments are linked to the dystrophin complex, which is itself anchored in the plasma membrane, while the TAN lines do a similar role, but connecting to the nuclear membrane.
TAN lines in the nucleus
Could these structures be involved in the development of certain neuromuscular diseases?
The integrity of this transmembrane structure is critical for nuclear movement: we have demonstrated that the inhibition of any of these three proteins inhibits nuclear movement.
 
< In red, the TAN lines on the surface of the nucleus can be seen in the photo.

 
Moreover, it was shown that mutations in different members of this structure were found in Emery-Dreyfuss muscular dystrophy, in laminopathies or in some cardiomyopathies. But the link between the nuclear position and the disease has not yet been elucidated. However, it is very common to see nuclei at the centre of muscle fibres in patients, whereas the nuclei are normally at the periphery.
 
What are the next steps?
These results were obtained in fibroblasts. We will thus start by analyzing muscle cells to see whether this structure exists and if it has the same behaviour, first in mouse cells then in healthy and dystrophic human cells. In parallel, we are investigating whether mutations in nuclear envelope proteins isolated by screening could have a role in muscular dystrophies.
Finally, in the even longer term, we would like to establish collaborations with other teams of the Institute of Myology (Gisèle Bonne, Luis Garcia, among others) to try and repair mutations, to ultimately improve the lives of patients.
 
September 2010
Interview by Anne Berthomier, translation by Racquel N. Cooper

 
*G. W. G. Luxton (1), E. R. Gomes (1), E. S. Folker, E. Vintinner, G. G. Gundersen,
Linear Arrays of Nuclear Envelope Proteins Harness Retrograde Actin Flow for Nuclear Movement,
Science 329, 956 (2010).

(1) Co-authors