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: Cristina Capanni, Stefano Squarzoni, Vittoria Cenni, Maria Rosaria D'Apice, Alessandra Gambineri, Giuseppe Novelli, Manfred Wehnert, Renato Pasquali, Nadir M Maraldi, Giovanna Lattanzi
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 11 Issue 19 Pg. 3568-77 (Oct 01 2012) ISSN: 1551-4005 [Electronic] United States
• PMID: 22935701 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BANF1 protein, human
• DNA-Binding Proteins
• Lamin Type A
• Membrane Proteins
• Mutant Proteins
• Nuclear Proteins
• Protein Precursors
• emerin
• prelamin A

Topics

• Acro-Osteolysis (metabolism, pathology)
• Adult
• Animals
• Cell Nucleus (metabolism)
• Contracture (metabolism, pathology)
• DNA-Binding Proteins (metabolism)
• HEK293 Cells
• Humans
• Infant, Newborn
• Lamin Type A
• Lipodystrophy (metabolism, pathology)
• Lipodystrophy, Familial Partial (metabolism, pathology)
• Mandible (abnormalities, metabolism, pathology)
• Membrane Proteins (metabolism)
• Mutant Proteins (metabolism)
• Nuclear Proteins (metabolism)
• Protein Binding
• Protein Precursors (metabolism)
• Protein Transport
• Rats
• Skin Abnormalities (metabolism, pathology)
• Transfection