Lamin A precursor induces barrier-to-autointegration factor nuclear localization.
Lamin A, a protein component of the nuclear lamina, is synthesized as a precursor named prelamin A, whose multi-step maturation process involves different protein intermediates. As demonstrated in laminopathies such as familial partial lipodystrophy, mandibuloacral dysplasia, Werner syndrome, Hutchinson-Gilford progeria syndrome and restrictive dermopathy, failure of prelamin A processing results in the accumulation of lamin A protein precursors inside the nucleus which dominantly produces aberrant chromatin structure. To understand if nuclear lamina components may be involved in prelamin A chromatin remodeling effects, we investigated barrier-to-autointegration factor (BAF) localization and expression in prelamin A accumulating cells. BAF is a DNA-binding protein that interacts directly with histones, lamins and LEM-domain proteins and has roles in chromatin structure, mitosis and gene regulation. In this study, we show that the BAF heterogeneous localization between nucleus and cytoplasm observed in HEK293 cycling cells changes in response to prelamin A accumulation. In particular, we observed that the accumulation of lamin A, non-farnesylated prelamin A and farnesylated carboxymethylated lamin A precursors induce BAF nuclear translocation. Moreover, we show that the treatment of human fibroblasts with prelamin A interfering drugs results in similar changes. Finally, we report that the accumulation of progerin, a truncated form of farnesylated and carboxymethylated prelamin A identified in Hutchinson-Gilford progeria syndrome cells, induces BAF recruitment in the nucleus. These findings are supported by coimmunoprecipitation of prelamin A or progerin with BAF in vivo and suggest that BAF could mediate prelamin A-induced chromatin effects.
Capanni
Cristina
C
IGM-CNR, Unit of Bologna c/o IOR, Bologna, Italy. ccapanni@area.bo.cnr.it
Cenni
Vittoria
V
Haraguchi
Tokuko
T
Squarzoni
Stefano
S
Schüchner
Stefan
S
Ogris
Egon
E
Novelli
Giuseppe
G
Maraldi
Nadir
N
Lattanzi
Giovanna
G
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D034904:Lamin Type A; D009687:Nuclear Proteins / Q000378:metabolism*; D011371:Progeria / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051381:Rats
C501959:BANF1 protein, human; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A