The nuclear envelope LEM-domain protein emerin

Abstract

Emerin, a conserved LEM-domain protein, is among the few nuclear membrane proteins for which extensive basic knowledge—biochemistry, partners, functions, localizations, posttranslational regulation, roles in development and links to human disease—is available. This review summarizes emerin and its emerging roles in nuclear “lamina” structure, chromatin tethering, gene regulation, mitosis, nuclear assembly, development, signaling and mechano-transduction. We also highlight many open questions, exploration of which will be critical to understand how this intriguing nuclear membrane protein and its “family” influence the genome.

Emerin intermolecular links to emerin and BAF

“…Previous work has shown lamin A binding is disrupted by centrally located mutations in emerin (residues 70-170) (Berk et al, 2013b;Lee et al, 2001). We challenged this result by identifying regions of emerin sufficient to bind lamin tails in vitro.…”

“…Human emerin binds proteins that are crucial for centrosome positioning and nuclear envelope structure (SUN1, SUN2, and nesprins) (Haque et al, 2010;Salpingidou et al, 2007) and influences actin cytoskeletal dynamics (Chang et al, 2013;Ho et al, 2013;Holaska et al, 2004). Emerin activates HDAC3, inhibits b-catenin and LMO7 (Berk et al, 2013b;Demmerle et al, 2012;Holaska et al, 2006;Markiewicz et al, 2006), helps 'tether' silent chromatin (Amendola and van Steensel, 2014), and is required to activate force-responsive genes ('mechano-transduction signaling') (Lammerding et al, 2005).…”

O-Linked β-N-Acetylglucosamine (O-GlcNAc) Regulates Emerin Binding to Barrier to Autointegration Factor (BAF) in a Chromatin- and Lamin B-enriched “Niche”

“…Five O-GlcNAc sites (Ser-54, Ser-57, Ser-58, Ser-171, and Ser-173) are also reportedly phosphorylated (44), suggesting that OGT competes with unknown kinases to control emerin during both mitosis (105) and interphase (e.g. EGF stimulates phosphorylation at Ser-54, Ser-58, Ser-171, and Ser-173) (106,107).…”

“…By contrast, the paucity of emerin-BAF association in the easy fraction, where A-type lamins were also abundant, suggests that all three proteins have alternative functions in the easy niche. Potential alternative functions include roles in signaling, proliferation, epigenetic regulation, and association with other nucleoskeletal components (1,44,83). These two fractions significantly extend the nuclear matrix and nucleoskeleton as operational concepts by separating the nuclear membrane protein emerin and other nuclear lamina proteins based on their association with the genome; B-type lamins and a subset of emerin, BAF, and A-type lamins partition with chromatin, whereas easy emerin, BAF, and A-type lamins are either fully chromatin-independent or associate with trace amounts of chromatin (H3) present in this fraction.…”

“…Emerin is highly modified by Ser/Thr and Tyr phosphorylation during interphase and mitosis (44,45). Emerin also has features (rich in Ser/Thr residues; large regions of predicted disorder) characteristic of proteins modified by O-linked ␤-Nacetylglucosamine (O-GlcNAc) (46 -48), a single sugar modification of Ser or Thr residues that is abundant, reversible, and dynamic.…”