| First Author | Meyer AJ | Year | 2011 |
| Journal | J Cell Sci | Volume | 124 |
| Issue | Pt 9 | Pages | 1433-44 |
| PubMed ID | 21486941 | Mgi Jnum | J:182955 |
| Mgi Id | MGI:5317235 | Doi | 10.1242/jcs.077883 |
| Citation | Meyer AJ, et al. (2011) Structural protein 4.1R is integrally involved in nuclear envelope protein localization, centrosome-nucleus association and transcriptional signaling. J Cell Sci 124(Pt 9):1433-44 |
| abstractText | The multifunctional structural protein 4.1R is required for assembly and maintenance of functional nuclei but its nuclear roles are unidentified. 4.1R localizes within nuclei, at the nuclear envelope, and in cytoplasm. Here we show that 4.1R, the nuclear envelope protein emerin and the intermediate filament protein lamin A/C co-immunoprecipitate, and that 4.1R-specific depletion in human cells by RNA interference produces nuclear dysmorphology and selective mislocalization of proteins from several nuclear subcompartments. Such 4.1R-deficiency causes emerin to partially redistribute into the cytoplasm, whereas lamin A/C is disorganized at nuclear rims and displaced from nucleoplasmic foci. The nuclear envelope protein MAN1, nuclear pore proteins Tpr and Nup62, and nucleoplasmic proteins NuMA and LAP2alpha also have aberrant distributions, but lamin B and LAP2beta have normal localizations. 4.1R-deficient mouse embryonic fibroblasts show a similar phenotype. We determined the functional effects of 4.1R-deficiency that reflect disruption of the association of 4.1R with emerin and A-type lamin: increased nucleus-centrosome distances, increased beta-catenin signaling, and relocalization of beta-catenin from the plasma membrane to the nucleus. Furthermore, emerin- and lamin-A/C-null cells have decreased nuclear 4.1R. Our data provide evidence that 4.1R has important functional interactions with emerin and A-type lamin that impact upon nuclear architecture, centrosome-nuclear envelope association and the regulation of beta-catenin transcriptional co-activator activity that is dependent on beta-catenin nuclear export. |
