The nucleoporin ELYS/Mel28 regulates nuclear envelope subdomain formation in HeLa cells

Abstract

In open mitosis the nuclear envelope (NE) reassembles at the end of each mitosis. This process involves the reformation of the nuclear pore complex (NPC), the inner and outer nuclear membranes, and the nuclear lamina. In human cells cell cycle-dependent NE subdomains exist, characterized as A-type lamin-rich/NPC-free or B-type lamin-rich/NPC-rich, which are initially formed as core or noncore regions on mitotic chromosomes, respectively. Although postmitotic NE formation has been extensively studied, little is known about the coordination of NPC and NE assembly. Here, we report that the nucleoporin ELYS/Mel28, which is crucial for postmitotic NPC formation, is essential for recruiting the lamin B receptor (LBR) to the chromosomal noncore region. Furthermore, ELYS/Mel28 is responsible for focusing of A-type lamin-binding proteins like emerin, Lap2α and the barrier-to-autointegration factor (BAF) at the chromosomal core region. ELYS/Mel28 biochemically interacts with the LBR in a phosphorylation-dependent manner. Recruitment of the LBR depends on the nucleoporin Nup107, which interacts with ELYS/Mel28 but not on nucleoporin Pom121, suggesting that the specific molecular interactions with ELYS/Mel28 are involved in the NE assembly at the noncore region. The depletion of the LBR affected neither the behavior of emerin nor Lap2α indicating that the recruitment of the LBR to mitotic chromosomes is not involved in formation of the core region. The depletion of ELYS/Mel28 also accelerates the entry into cytokinesis after recruitment of emerin to chromosomes. Our data show that ELYS/Mel28 plays a role in NE subdomain formation in late mitosis.

HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 Is Required for Circadian Periodicity through the Promotion of Nucleo-Cytoplasmic mRNA Export in Arabidopsis

“…SAR1, LOS4, and NUA are all required for correct mRNA nuclear export (Cernac et al, 1997;Gong et al, 2002Gong et al, , 2005Dong et al, 2006b;Parry et al, 2006;Xu et al, 2007), and NUP107 is a structural nucleoporin that is part of the evolutionarily conserved Nup107-Nup160 subcomplex with SAR1 (Tamura et al, 2010;Clever et al, 2012). In a manner resembling hos1 mutants, loss of any of these genes led to a long period, as measured by delayed fluorescence ( Figure 6A).…”

Phosphoinositide 3-Kinase Beta Protects Nuclear Envelope Integrity by Controlling RCC1 Localization and Ran Activity

“…Some details are missing from this model, although others have been clearly demonstrated. For instance, Ran-GTP generated at chromosomes regulates NPC assembly by releasing Nup complexes from Imp␤ (60,61). It is less clear how Ran-GTP levels increase at the end of mitosis to trigger NE/NPC formation, although the decrease of RanBP1 in advanced telophase (62) might help to increase Ran-GTP levels in late mitosis; such an increase would then permit Nup complex binding to chromatin, pre-NPC and NPC formation, and vesicle fusion.…”

“…Nup intermolecular interactions were perturbed in mitosis and interphase, suggesting that PI3K␤ acts in a common step needed for NPC formation in both phases. Since Ran-GTP regulates the formation of Nup complexes on the chromatin and NPC assembly in mitosis and interphase (16,60,61), it is tempting to speculate that PI3K␤ controls NPC formation by regulating Ran activation.…”

“…Nonetheless, MEL28 localization and function are also regulated by Ran-GTP (16,61). Nup components thus affect NE and lamina formation in a Ran-dependent manner.…”

“…It is less clear how Ran-GTP levels increase at the end of mitosis to trigger NE/NPC formation, although the decrease of RanBP1 in advanced telophase (62) might help to increase Ran-GTP levels in late mitosis; such an increase would then permit Nup complex binding to chromatin, pre-NPC and NPC formation, and vesicle fusion. By regulating components such as Mel28, Ran-GTP would also affect lamin B receptor and lamin B recruitment to the chromosome periphery and nuclear lamina formation (61).…”