[en] Facioscapulohumeral dystrophy (FSHD) is a degenerative disease of skeletal muscle caused by chromatin opening and DNA hypomethylation at the D4Z4 repeat array in the 4q35 subtelomeric region. The open chromatin facilitates the expression of the DUX4 (Double Homeobox 4) gene that is located in the D4Z4 element. This gene encodes a transcription factor initiating a cascade of deregulation affecting many genes and that causes the disease.
Recently, our laboratory (in collaboration with Dpt of Proteomics and Microbiology UMONS) has compared the proteome of primary FSHD and control myotubes at day 4 of differentiation. Both FSHD myotube phenotypes presented a disturbance of several caveolar proteins such as PTRF (polymerase I and transcript release factor, cavin-1) and MURC (muscle-related coiled-coil protein, cavin-4). Caveolae are membrane nanodomains, often considered as a subset of lipid rafts, enriched in cholesterol and sphingolipids. They are also characterized by a specific protein composition. Caveolae play a major role in signal transduction and are involved in many biological processes. If caveolar dysfunction can be demonstrated in FSHD as suggested by our preliminary results, deregulation of MURC and PTRF proteins, that are essentials for membrane stability of skeletal muscle, could lead to deregulation of many cellular processes.
In addition, if a link between DUX4 and this caveolar dysfunction can be shown, these proteins could be used as additional FSHD biomarkers. Identification of FSHD biomarkers and their validation is essential to assess the therapeutic approach developed by our laboratory i.e. antisense tools preventing DUX4 expression.
Research center :
CREMH - Mind & Health
Disciplines :
General & internal medicine
Author, co-author :
Wauters, Armelle ; Université de Mons > Faculté de Médecine et de Pharmacie > Biochimie métabolique et moléculaire
Tassin, Alexandra ; Université de Mons > Faculté de Médecine et de Pharmacie > Biochimie métabolique et moléculaire
Leroy, Baptiste ; Université de Mons > Faculté des Sciences > Protéomie et Microbiologie
Laval, Steven
Wattiez, Ruddy ; Université de Mons > Faculté des Sciences > Protéomie et Microbiologie
Coppée, Frédérique ; Université de Mons > Faculté de Médecine et de Pharmacie > Service de Biochimie métabolique et moléculaire
Belayew, Alexandra ; Université de Mons > Faculté de Médecine et de Pharmacie > Biochimie métabolique et moléculaire
Language :
English
Title :
Caveolar proteins: putative FSHD biomarkers?
Publication date :
29 January 2013
Number of pages :
1
Event name :
', Journée de l'école doctorale en sciences biomédicales et pharmaceutiques, UMONS
Event place :
Mons, Belgium
Event date :
2013
Research unit :
M122 - Biochimie métabolique et moléculaire
Research institute :
R550 - Institut des Sciences et Technologies de la Santé