title: Familial partial lipodystrophy, mandibuloacral dysplasia and restrictive dermopathy feature barrier-to-autointegration factor (BAF) nuclear redistribution.
abstract: Prelamin A processing impairment is a common feature of a restricted group of rare genetic alterations/disorders associated with a wide range of clinical phenotypes. Changes in histone posttranslational modifications, alterations in non-histone chromatin proteins and chromatin disorganization have been specifically linked to impairment of specific, distinct prelamin A processing steps, but the molecular mechanism involved in these processes is not yet understood . In this study, we show that the accumulation of wild-type prelamin A detected in restrictive dermopathy (RD), as well as the accumulation of mutated forms of prelamin A identified in familial partial lipodystrophy (FPLD) and mandibuloacral dysplasia (MADA), affect the nuclear localization of barrier-to-autointegration factor (BAF), a protein able to link lamin A precursor to chromatin remodeling functions. Our findings, in accordance with previously described results, support the hypothesis of a prelamin A involvement in BAF nuclear recruitment and suggest BAF-prelamin A complex as a protein platform usually activated in prelamin A-accumulating diseases. Finally, we demonstrate the involvement of the inner nuclear membrane protein emerin in the proper localization of BAF-prelamin A complex.
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna-IOR, Bologna, Italy. ccapanni@area.bo.cnr.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Capanni
authors.forename: Stefano
authors.initials: S
authors.lastname: Squarzoni
authors.forename: Vittoria
authors.initials: V
authors.lastname: Cenni
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: D'Apice
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gambineri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Manfred
authors.initials: M
authors.lastname: Wehnert
authors.forename: Renato
authors.initials: R
authors.lastname: Pasquali
authors.forename: Nadir M
authors.initials: NM
authors.lastname: Maraldi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lattanzi
mesh_terms: D030981:Acro-Osteolysis / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003286:Contracture / Q000378:metabolism* / Q000473:pathology / Q000151:congenital; D004268:DNA-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007231:Infant, Newborn; D034904:Lamin Type A; D008060:Lipodystrophy / Q000378:metabolism* / Q000473:pathology; D052496:Lipodystrophy, Familial Partial / Q000378:metabolism* / Q000473:pathology; D008334:Mandible / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D012868:Skin Abnormalities / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: C501959:BANF1 protein, human; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D008565:Membrane Proteins; D050505:Mutant Proteins; D009687:Nuclear Proteins; D011498:Protein Precursors; C092710:emerin; C090764:prelamin A