Inner nuclear membrane protein transport is mediated by multiple mechanisms

Zuleger, Nikolaj; Korfali, Nadia; Schirmer, Eric C.

doi:10.1042/bst0361373

Cited by 34 publications

(32 citation statements)

References 44 publications

(51 reference statements)

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“…The reduced NE expression of emerin, together with its mislocalization into the ER and formation of aggregates with mutant LUMA, indicates that M2 LUMA oligomers might prevent emerin from localizing to NE properly. So far, the intracellular trafficking and nuclear localization of emerin is still not clarified, [24][25][26] although it might be affected by the deficiency of A-type lamins and nesprins. 4,27 Our findings suggest that LUMA may also be a determinant for the proper nuclear localization of emerin.…”

Section: Discussionmentioning

confidence: 99%

TMEM43 mutations in emery‐dreifuss muscular dystrophy‐related myopathy

Liang

Mitsuhashi

Keduka

et al. 2011

Annals of Neurology

109

103

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Section: Discussionmentioning

confidence: 99%

TMEM43 mutations in emery‐dreifuss muscular dystrophy‐related myopathy

Liang

Mitsuhashi

Keduka

et al. 2011

Annals of Neurology

109

103

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“…The cation channel DMI1 is necessary for symbiotic calcium oscillations, and we show that this channel is preferentially located on the inner nuclear membrane, implying an essential function for this membrane in the activation of the calcium oscillations. The targeting of DMI1 to the inner nuclear membrane may explain the requirement for components of the nuclear pore in symbiosis signaling (11)(12)(13)(14), because the nuclear pore seems to be involved in flipping proteins between the outer and inner nuclear membranes (18).…”

Section: Discussionmentioning

confidence: 99%

“…The outer nuclear membrane is contiguous with the endoplasmic reticulum (ER), but the inner nuclear membrane is a specialized membrane connected to the outer membrane through the nuclear pore. Integral membrane proteins targeted to this membrane require nuclear localization signals (NLS): it has been suggested that the nuclear pore is involved in translocating membrane proteins containing an NLS from the outer to the inner nuclear membrane (18).…”

mentioning

confidence: 99%

Nuclear membranes control symbiotic calcium signaling of legumes

Capoen

Sun

Wysham

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

188

170

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Nuclear-associated oscillations in calcium act as a secondary messenger in the symbiotic signaling pathway of legumes. These are decoded by a nuclear-localized calcium and calmodulin-dependent protein kinase, the activation of which is sufficient to drive downstream responses. This implies that the calcium oscillations within the nucleus are the predominant signals for legume symbiosis. However, the mechanisms that allow targeted release of calcium in the nuclear region have not been defined. Here we show that symbiosis-induced calcium changes occur in both the nucleoplasm and the perinuclear cytoplasm and seem to originate from the nuclear membranes. Reaction diffusion simulations suggest that spike generation within the nucleoplasm is not possible through transmission of a calcium wave from the cytoplasm alone and that calcium is likely to be released across the inner nuclear membrane to allow nuclear calcium changes. In agreement with this, we found that the cation channel DMI1, which is essential for symbiotic calcium oscillations, is preferentially located on the inner nuclear membrane, implying an essential function for the inner nuclear membrane in symbiotic calcium signaling. Furthermore, a sarco/endoplasmic reticulum calcium ATPase (SERCA) essential for symbiotic calcium oscillations is targeted to the inner nuclear membrane, as well as the outer nuclear membrane and endoplasmic reticulum (ER). We propose that release of calcium across the inner nuclear membrane allows targeted release of the ER calcium store, and efficient reloading of this calcium store necessitates the capture of calcium from the nucleoplasm and nuclear-associated cytoplasm.L egumes form mutualistic symbiotic interactions with mycorrhizal fungi and with rhizobial bacteria that aid in the uptake of nutrients (1, 2). Establishment of both symbioses requires the common symbiosis (Sym) signaling pathway (1, 2) that involves calcium oscillations after perception of diffusible signals from the symbionts (3, 4): Nod factors from rhizobia and Myc factors from mycorrhizal fungi (4-7). The calcium oscillations are concentrated in the perinuclear region (3), and a nuclear-targeted calcium reporter showed that part of these oscillations occurs in the nucleoplasm (8). The decoder of the calcium oscillations, a calcium and calmodulin-dependent protein kinase (CCaMK), is localized to the nucleoplasm (9, 10), implying that intranuclear calcium changes are paramount. Furthermore, some of the components of the Sym pathway required for the induction of calcium oscillations are localized to the nuclear envelope: two cation channels and three components of the nuclear pore (11-14). All of this points to the nuclear membrane as playing a central role in symbiotic calcium oscillations.The question of whether calcium changes can derive from the nucleus has been a contentious point for many years (15, 16). In animals, it is widely accepted that calcium events in and around the nucleus have significant effects on signaling pathways in the nucleus (15). Depend...

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“…lamin B receptor (LBR)) (20,21). This model suggests that proteins synthesized in the ER rapidly diffuse laterally in the ONM, pass through peripheral channels existing between the nuclear pore complex and the pore membrane, and then become tethered in the INM via nucleoplasmic interactions with nuclear lamins or chromatin (22)(23)(24). Because the peripheral channels are thought to be about 10 nm, nucleoplasmic domains cannot exceed masses of Ͼ60 kDa (25)(26)(27).…”

Section: Edited By Roger J Colbranmentioning

confidence: 99%

Sequences within the C Terminus of the Metabotropic Glutamate Receptor 5 (mGluR5) Are Responsible for Inner Nuclear Membrane Localization

Jong¹,

Harmon

Kumar

et al. 2017

Journal of Biological Chemistry

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Edited by Roger J. ColbranTraditionally, G-protein-coupled receptors (GPCR) are thought to be located on the cell surface where they transmit extracellular signals to the cytoplasm. However, recent studies indicate that some GPCRs are also localized to various subcellular compartments such as the nucleus where they appear required for various biological functions. For example, the metabotropic glutamate receptor 5 (mGluR5) is concentrated at the inner nuclear membrane (INM) where it mediates Ca 2؉ changes in the nucleoplasm by coupling with G q/11 . Here, we identified a region within the C-terminal domain (amino acids 852-876) that is necessary and sufficient for INM localization of the receptor. Because these sequences do not correspond to known nuclear localization signal motifs, they represent a new motif for INM trafficking. mGluR5 is also trafficked to the plasma membrane where it undergoes re-cycling/degradation in a separate receptor pool, one that does not interact with the nuclear mGluR5 pool. Finally, our data suggest that once at the INM, mGluR5 is stably retained via interactions with chromatin. Thus, mGluR5 is perfectly positioned to regulate nucleoplasmic Ca 2؉ in situ.From their position on the cell surface, G-protein-coupled receptors (GPCRs) 3 can transform external stimuli into a broad range of signaling pathways within the cell. A mounting body of evidence indicates that many GPCRs are also localized inside the cell where they may couple to different signaling systems, display unique desensitization patterns, and/or exhibit distinct patterns of subcellular distribution (1-5). For example, GPCRs have been found on mitochondria (6), endoplasmic reticulum (ER) membranes (7), lysosomes (8, 9), and on nuclear membranes (10 -12). Certain GPCRs are even found within the nucleoplasm on nuclear bodies and/or nuclear invaginations (13-16). Although many intracellular GPCRs are activated at the cell surface and subsequently trafficked to their intracellular site, others can be activated at their subcellular location via so-called intracrine ligands that can enter cells via diffusion or be made in situ, endocytosed, and/or transported through channels or pores (12,17,18). Intracellular GPCRs can also function independently governing processes such as synaptic plasticity (19), myocyte contraction (15), and angiogenesis (16). Collectively, the present findings reinforce the notion that intracellular GPCRs play a dynamic role in generating and shaping intracellular signaling pathways.As many GPCRs are on or in the nucleus, the question arises as to how they get there. Various possibilities exist to transfer membrane proteins from the outer to the inner nuclear membrane (ONM and INM), including vesicle fusion, membrane rupture, and channel-mediated pathways. Most prominently, a diffusion-retention model has been proposed for many INM proteins (e.g. lamin B receptor (LBR)) (20,21). This model suggests that proteins synthesized in the ER rapidly diffuse laterally in the ONM, pass through peripheral channels ex...

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Inner nuclear membrane protein transport is mediated by multiple mechanisms

Cited by 34 publications

References 44 publications

TMEM43 mutations in emery‐dreifuss muscular dystrophy‐related myopathy

TMEM43 mutations in emery‐dreifuss muscular dystrophy‐related myopathy

Nuclear membranes control symbiotic calcium signaling of legumes

Sequences within the C Terminus of the Metabotropic Glutamate Receptor 5 (mGluR5) Are Responsible for Inner Nuclear Membrane Localization

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