The dynamism of PABPN1 nuclear inclusions during the cell cycle.
Oculopharyngeal muscular dystrophy (OPMD) is caused by expansion of a (GCN)10 to a (GCN)11-17 repeat coding for a polyalanine domain at the N-terminal part of poly(A) binding protein nuclear 1 (PABPN1). OPMD is characterized by the presence of intranuclear inclusions (INIs) in skeletal muscle fibers of patients. The formation of GFP-b13AlaPABPN1 INIs and their fate through the cell cycle were followed by time-lapse imaging. Our observations demonstrated that the GFP-b13AlaPABPN1 INIs are dynamic structures that can disassemble during mitosis. However, their presence in cells occasionally led to apoptosis. The length of the polyalanine tail or the overexpression of PABPN1 did not significantly affect the percentage of soluble PABPN1 in vitro. Moreover, overexpression of either the wild type (wt) or mutant (mut) forms of PABPN1 slowed down the cell proliferation. The slowing down of proliferation together with the occasional occurrence of apoptosis could contribute in vivo to the late onset of this disease.
Marie-Josée Sasseville
A
A
Laboratoire de Neurogénétique, Centre de Recherche du CHUM, Université de Montréal, Montréal, Québec, Canada H2L 4M1.
Caron
Antoine W
AW
Bourget
Lucie
L
Klein
Arnaud F
AF
Dicaire
Marie-Josée
MJ
Rouleau
Guy A
GA
Massie
Bernard
B
Langelier
Yves
Y
Brais
Bernard
B
D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008938:Mitosis / Q000235:genetics; D039141:Muscular Dystrophy, Oculopharyngeal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000378:metabolism; D039122:Poly(A)-Binding Protein I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology
D010455:Peptides; D039122:Poly(A)-Binding Protein I; C019529:polyalanine