Interplay of the nuclear envelope with chromatin in physiology and pathology

Abstract

The nuclear envelope compartmentalizes chromatin in eukaryotic cells. The main nuclear envelope components are lamins that associate with a panoply of factors, including the LEM domain proteins. The nuclear envelope of mammalian cells opens up during cell division. It is reassembled and associated with chromatin at the end of mitosis when telomeres tether to the nuclear periphery. Lamins, LEM domain proteins, and DNA binding factors, as BAF, contribute to the reorganization of chromatin. In this context, an emerging role is that of the ESCRT complex, a machinery operating in multiple membrane assembly pathways, including nuclear envelope reformation. Research in this area is unraveling how, mechanistically, ESCRTs link to nuclear envelope associated factors as LEM domain proteins. Importantly, ESCRTs work also during interphase for repairing nuclear envelope ruptures. Altogether the advances in this field are giving new clues for the interpretation of diseases implicating nuclear envelope fragility, as laminopathies and cancer.

Zika virus NS4A hijacks host ANKLE2 to promote viral replication

“…Plentiful other ANKLE2-host protein interactions have been found in large proteomic screens (59)(60)(61)(62). Presumably the bulk of these interactions are mediated through its ANK domain, which facilitates scaffolding functions in many proteins (63,64), or by the LEM domain, which is known to mediate interaction with the inner nuclear membrane lamina and BANF1 (65)(66)(67). It is particularly appealing to speculate that ZIKV leverages the protein interaction/scaffolding function of ANKLE2 to facilitate protein interactions within replication compartments.…”

Nuclear Dynamics and Chromatin Structure: Implications for Pancreatic Cancer

“…Large multiprotein structures, the nuclear pore complexes, span the nuclear envelope. Just interior to the INM is the nuclear lamina, a dense protein meshwork consisting of lamins and associated proteins that plays key roles in tethering heterochromatin to the nuclear periphery [18,19]. The ONM is continuous with the endoplasmic reticulum (ER) and retains many proteins in common with the ER [20,21].…”

“…The INM is known to contain >60 proteins, only some of which are characterized [16,21]. One important group of INM proteins is the LEM family, which contain the LAP2-Emerin-MAN1 (LEM) domain, a region that binds to the Barrier to Autointegration Factor (BANF1) (Figure 1) [18,21,29]. Mammals have seven genes encoding LEM proteins, including Emerin, LAP2 (gene name TMPO, encodes multiple splice forms including LAP2α and LAP2β), MAN1, LEMD1, LEMD2, ANKLE1, and ANKLE2 [30][31][32][33][34].…”

“…Although not all LEM protein functions are well-characterized, each of these proteins appear to be involved in nuclear membrane architecture or maintenance, and/or mitotic processes. Most importantly for our discussion, LEM proteins are well-known regulators of nuclear architecture, via tethering heterochromatin to the nuclear periphery either directly or indirectly through BANF1 [18,21,35,36]. Not all mammalian cells and tissues contain the same assortment of LEM proteins, and their functions are thought to be distinct, although some may be partially redundant [31,37].…”

Role of Lamin A and emerin in maintaining nuclear morphology in different subtypes of ovarian epithelial cancer

“…Beneath the inner nuclear membrane, the nuclear lamina meshwork structure is formed to give the nucleus strength and elasticity ( 2 ). The nuclear lamina is composed of intermediate filaments (Lamin A, B or C) ( 3 ). It has been reported that nuclear shape abnormalities are more frequently observed in mouse embryonic fibroblasts featuring Lamin A deletion than those featuring deletion of Lamin B or C ( 4 ).…”