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NE-Organisation
NE- Proteomics
The INM-Protein LUMA
Phosphorylation at the NE
Allgemein:
The nuclear envelope consists of two membranes interconnected to each other, which are part of the endoplasmic reticulum (ER) and separate the cytoplasm from the ER-lumen and the nulear interior. The exchange of macromolecules is controlled by nuclear pore complexes, large protein complexes structuring the nucler pores, where outer and inner nuclear membrane are connected. The inside of the nuclear envelope is lined and stabilized by lamin intermediate filaments, which in addition to structurally supporting the nuclear membranes provide anchor points for binding nuclear proteins. These interactions turned out to be remarkably relevant for cellular health. Many genetic diseases called laminopathies result from disturbed interactions of nuclear proteins with A-type lamins. [more ...]
Abbildung: Structure of the nuclear envelope - CHROM: chromatin; INM: inner nuclear membrane; LAM: lamina; NPC: nuclear pore complex; ONM: outer nuclear membrane.
Up to the end of the 1990s, not more than a handful of proteins were known to reside specifically at the inner nuclear membrane. Most of these proteins had been identified by their capability to bind lamins with high affinity. In an effort to identify more proteins of the nuclear envelope to get to know the players at the envelope and their substructures, we started a subcellular proteomics screen for novel components of the nuclear envelope. We could successfully identify a few new members of nuclear membrane proteins, namely two isoforms of the LAP-2 family, the SUN-proteins SUN-1 and SUN-2 and a novel protein,w hich we called LUMA. [more ...]
Abbildung: Categories of Nuclear Membrane Proteins - The different categories of nuclear membrane proteins, distinguished by their specific localisation to one of the NE substructure, and their putative interactions are displayed. ER: endoplasmic reticulum; INM: inner nuclear membrane; LAM: lamina; ONM: outer nuclear membrane.
In our proteomics screen on purified nuclear envelopes we identified the 45-kDa-protein LUMA as a protein of the inner nuclear membrane. LUMA is a novel protein present in many species, even in plants and in some bacteria. A more detailed characterization shows that only a part of the LUMA pool is retained at the inner nuclear membrane. In some cell types, a remarkably high amount of LUMA is present in other domains of the ER. LUMA homo-oligomerizes, binds to emerin and depends on A-type lamins for its inner-nuclear-membrane targeting. We propose that LUMA is a tetraspanin-like membrane organizer, which may be linked belonging to the nuclear-envelopathy family of diseases . [more ...]
Abbildung: LUMATopology and Interactions - LUMA oligomerizes and interacts with emerin. Both interactions depend on LUMA transmembrane domains.
The reversible phosphorylation of proteins a a major tool of eukaryotic cells to control and regulate cellular processes. Phosphorylation of lamins, for example, is used to dissolve the nuclear envelope structure in cells undergoing an open form of mitosis. We were interested in phosphorylation events at the nuclear envelope as part of the signal transduction / signal integration mechanisms of cells. We demonstrated the interphase phosphorylation of LAP2-beta at serine and threonine residues. Remarkably, a number of nuclear-envelope proteins is subject to tyrosine phosphorylation. We could recently show that a major target for tyrosine phosphorylation is emerin, a protein in the center of structuring lamin-chromatin interactions, which is linked to the development of Emery-Dreifuss muscle dystrophy. [more ...]
Abbildung: Putative Phosphorylation-Dependent LAP2-beta Inter - Sketch of conceivable interactions of the INM-protein LAP2-beta at the inner face of the nuclear envelope.
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Henning Otto / updated: 12.04.2011