Fission yeast Lem2 and Man1 perform fundamental functions of the animal cell nuclear lamina

Abstract

In animal cells the nuclear lamina, which consists of lamins and lamin-associated proteins, serves several functions: it provides a structural scaffold for the nuclear envelope and tethers proteins and heterochromatin to the nuclear periphery. In yeast, proteins and large heterochromatic domains including telomeres are also peripherally localized, but there is no evidence that yeast have lamins or a fibrous nuclear envelope scaffold. Nonetheless, we found that the Lem2 and Man1 proteins of the fission yeast Schizosaccharomyces pombe, evolutionarily distant relatives of the Lap2/Emerin/Man1 (LEM) sub-family of animal cell lamin-associated proteins, perform fundamental functions of the animal cell lamina. These integral inner nuclear membrane localized proteins, with nuclear localized DNA binding Helix-Extension-Helix (HEH) domains, impact nuclear envelope structure and integrity, are essential for the enrichment of telomeres at the nuclear periphery and by means of their HEH domains anchor chromatin, most likely transcriptionally repressed heterochromatin, to the nuclear periphery. These data indicate that the core functions of the nuclear lamina are conserved between fungi and animal cells and can be performed in fission yeast, without lamins or other intermediate filament proteins.

Control of heterochromatin localization and silencing by the nuclear membrane protein Lem2

“…4E). The absence of Dsh1 hardly affects the distribution of Taz1-GFP, whereas loss of Lem2 causes a more frequent delocalization, in agreement with a recent report (Gonzalez et al 2012). Intriguingly, cells lacking both Dsh1 and Lem2 display an exacerbated phenotype (27% vs. 16% in lem2Δ for zone III; P < 0.05), resulting in a nearly random distribution of telomeres (Fig.…”

“…Lem2 also contributes to telomere anchoring (Gonzalez et al 2012). We therefore tested whether Lem2 cooperates with the RNAi assembly factor Dsh1 in localization because of their redundancy in silencing.…”

“…These highly conserved domains project into the nucleoplasm, where they might interact with chromosomal regulatory factors. A recent study demonstrated that Lem2 and Man1 contribute to the integrity of the nuclear structure and to telomere anchoring in fission yeast (Gonzalez et al 2012). Furthermore, homologs of Lem2 associate with telomeric regions in Saccharomyces cerevisiae (Heh1/Src1) and Caenorhabditis elegans (LEM-2) (Grund et al 2008;Ikegami et al 2010), and loss of Heh1 causes defects in the perinuclear positioning of telomeres and the silent rDNA loci in budding yeast (Mekhail et al 2008;Chan et al 2011).…”

Unique and Shared Functions of Nuclear Lamina LEM Domain Proteins in Drosophila

“…Even though homology is limited, non-LEM-D regions of the Drosophila LEM-D proteins direct common protein associations, such as interactions with the A-and B-type lamins, Lamin C and lamin Dm 0 , respectively (Pinto et al 2008;Schulze et al 2009). These shared protein partners imply that Drosophila LEM-D proteins possess overlapping functions, as found for LEM-D proteins in other organisms (Gruenbaum et al 2002;Liu et al 2003;Huber et al 2009;Barkan et al 2012;Gonzalez et al 2012;Reil and Dabauvalle 2013). However, the extent of any regulatory compensation among the three Drosophila nuclear lamina LEM-D proteins is unknown.…”

Shape Transformation of the Nuclear Envelope during Closed Mitosis

“…2, will then drive the shape transformation of the nucleus by overcoming the elevated bending and surface energies stored in the deformed membrane. Recent evidence has indeed shown that various inner nuclear membrane proteins such as Heh1, Heh2, and Ima1 can bind and anchor chromatids to the NE (28)(29)(30)(31). Thus, it is conceivable that such connection prevents chromosomes from sliding away from the nuclear membrane during their contact and ultimately allows the poleward force to be transmitted to the NE.…”