| First Author | Pilat U | Year | 2013 |
| Journal | J Cell Sci | Volume | 126 |
| Issue | Pt 8 | Pages | 1753-62 |
| PubMed ID | 23444379 | Mgi Jnum | J:200658 |
| Mgi Id | MGI:5508999 | Doi | 10.1242/jcs.115246 |
| Citation | Pilat U, et al. (2013) The muscle dystrophy-causing DeltaK32 lamin A/C mutant does not impair the functions of the nucleoplasmic lamin-A/C-LAP2alpha complex in mice. J Cell Sci 126(Pt 8):1753-62 |
| abstractText | A-type lamins are components of the nuclear lamina, a filamentous network of the nuclear envelope in metazoans that supports nuclear architecture. In addition, lamin A/C can also be found in the interior of the nucleus. This nucleoplasmic lamin pool is soluble in physiological buffer, depends on the presence of the lamin-binding protein, lamina-associated polypeptide 2alpha (LAP2alpha) and regulates cell cycle progression in tissue progenitor cells. DeltaK32 mutations in A-type lamins cause severe congenital muscle disease in humans and a muscle maturation defect in Lmna(DeltaK32/DeltaK32) knock-in mice. Mutant DeltaK32 lamin A/C protein levels were reduced and all mutant lamin A/C was soluble and mislocalized to the nucleoplasm. To test the role of LAP2alpha in nucleoplasmic DeltaK32 lamin A/C regulation and functions, we deleted LAP2alpha in Lmna(DeltaK32/DeltaK32) knock-in mice. In double mutant mice the Lmna(DeltaK32/DeltaK32)-linked muscle defect was unaffected. LAP2alpha interacted with mutant lamin A/C, but unlike wild-type lamin A/C, the intranuclear localization of DeltaK32 lamin A/C was not affected by loss of LAP2alpha. In contrast, loss of LAP2alpha in Lmna(DeltaK32/DeltaK32) mice impaired the regulation of tissue progenitor cells as in lamin A/C wild-type animals. These data indicate that a LAP2alpha-independent assembly defect of DeltaK32 lamin A/C is the predominant cause of the mouse pathology, whereas the LAP2alpha-linked functions of nucleoplasmic lamin A/C in the regulation of tissue progenitor cells are not affected in Lmna(DeltaK32/DeltaK32) mice. |
