Further assembly required: construction and dynamics of the endoplasmic reticulum network. EMBO Rep 11 (7):515-521

Cellular Neurology Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, 9000 Rockville Pike, Bethesda, MD 20892-3738, USA.
EMBO Reports (Impact Factor: 7.86). 07/2010; 11(7):515-21. DOI: 10.1038/embor.2010.92
Source: PubMed

ABSTRACT The endoplasmic reticulum (ER) is a continuous membrane system comprising the nuclear envelope, ribosome-studded peripheral sheets and an interconnected network of smooth tubules extending throughout the cell. Although protein biosynthesis, transport and quality control in the ER have been studied extensively, mechanisms underlying the notably diverse architecture of the ER have only emerged recently; this review highlights these new findings and how they relate to ER functional specializations. Several protein families, including reticulons and DP1/REEPs/Yop1, harbour hydrophobic hairpin domains that shape high-curvature ER tubules and mediate intramembrane protein interactions. Members of the atlastin/RHD3/Sey1 family of dynamin-related GTPases mediate the formation of three-way junctions that characterize the tubular ER network, and additional classes of hydrophobic hairpin-containing ER proteins interact with and remodel the microtubule cytoskeleton. Flat ER sheets have a different complement of proteins implicated in shaping, cisternal stacking and microtubule interactions. Finally, several shaping proteins are mutated in hereditary spastic paraplegias, emphasizing the particular importance of proper ER morphology and distribution for highly polarized cells.

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    • "Lipid species distributions may relate to the bending modulus of the parasite membranes including the PVM, TVN and MC, as lipids with larger or smaller head groups have been shown to prefer more or less pronounced membrane curvatures, respectively (Song and Waugh, 1993; Pan et al., 2009). Several protein families and intramembrane protein interactions are known to be involved in the structure and curvature of the ER in eukaryotic cells (Hu et al., 2009; Park and Blackstone, 2010). While they have yet to be characterized in malaria parasites, we hypothesize that such proteins may contribute to the architecture of the PVM, TVN and MC and that Fig. 6. "
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    ABSTRACT: Plasmodium falciparum (Pf) infection remodels the human erythrocyte with new membrane systems, including a modified host erythrocyte membrane (EM), a parasitophorous vacuole membrane (PVM), a tubulovesicular network (TVN), and Maurer's clefts (MC). Here we report on the relative cholesterol contents of these membranes in parasitized normal (HbAA) and hemoglobin S-containing (HbAS, HbAS) erythrocytes. Results from fluorescence lifetime imaging microscopy (FLIM) experiments with a cholesterol-sensitive fluorophore show that membrane cholesterol levels in parasitized erythrocytes (pRBC) decrease inwardly from the EM, to the MC/TVN, to the PVM, and finally to the parasite membrane (PM). Cholesterol depletion of pRBC by methyl-β-cyclodextrin treatment caused a collapse of this gradient. Lipid and cholesterol exchange data suggest that the cholesterol gradient involves a dilution effect from non-sterol lipids produced by the parasite. FLIM signals from the PVM or PM showed little or no difference between parasitized HbAA vs HbS-containing erythrocytes that differed in lipid content, suggesting that malaria parasites may regulate the cholesterol contents of the PVM and PM independently of levels in the host cell membrane. Cholesterol levels may affect raft structures and the membrane trafficking and sorting functions that support Pf survival in HbAA, HbAS and HbSS erythrocytes.
    Biology Open 05/2014; 3(6). DOI:10.1242/bio.20147732 · 2.42 Impact Factor
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    • "Although the INM and ONM are continuous with each other and are fused together via the pore membrane, they contain varying sets of proteins to fulfill different functions. The ONM is studded with ribosomes similar to the rough ER (rER) and is involved in protein synthesis (Park and Blackstone 2010). The ONM binds microtubules (MTs) and can act as a nucleation center of microtubules, which organize in microtubule organizing center (MTOC) at the basis of the mitotic spindle during cell division (Zhang and Dawe 2011; Masoud et al. 2013). "
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    ABSTRACT: Significant advances in understanding the plant nuclear envelope have been made over the past few years; indeed, knowledge of the protein network at the nuclear envelope is rapidly growing. One such network, the linker of nucleoskeleton and cytoskeleton (LINC) complex, is known in animals to connect chromatin to the cytoskeleton through the nuclear envelope. The LINC complex is made of Sad1/Unc84 (SUN) and Klarsicht/Anc1/Syne1 homology (KASH) proteins which have been recently characterized in plants. SUN proteins are located within the inner nuclear membrane, while the KASH proteins are included into the outer nuclear membrane. SUN and KASH domains interact and bridge the two nuclear membranes. In Arabidopsis, KASH proteins also interact with the tryptophan-proline-proline (WPP) domain-interacting tail-anchored protein 1 (WIT1), associated with the nuclear pore complex and with myosin XI-i which directly interacts with the actin cytoskeleton. Although evidence for a plant LINC complex connecting the nucleus to the cytoskeleton is growing, its interaction with chromatin is still unknown, but knowledge gained from animal models strongly suggests its existence in plants. Possible functions of the plant LINC complex in cell division, nuclear shape, and chromatin organization are discussed.
    Chromosome Research 05/2014; 22(2). DOI:10.1007/s10577-014-9419-7 · 2.69 Impact Factor
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    • "organelle that is structurally and functionally related to ER (Hegde and Ploegh 2010; Park and Blackstone 2010). Ubiquitin aggregation and Golgi fragmentation were detected in the neurons of transgenic rats at non-symptomatic stages. "
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    ABSTRACT: Protein inclusion is a prominent feature of neurodegenerative diseases including frontotemporal lobar degeneration (FTLD) that is characterized by the presence of ubiquitinated TDP-43 inclusion. Presence of protein inclusions indicates an interruption to protein degradation machinery or the overload of misfolded proteins. In response to the increase in misfolded proteins, cells usually initiate a mechanism called unfolded protein response (UPR) to reduce misfolded proteins in the lumen of endoplasmic reticules. Here, we examined the effects of mutant TDP-43 on the UPR in transgenic rats that express mutant human TDP-43 restrictedly in the neurons of the forebrain. Over-expression of mutant TDP-43 in rats caused prominent aggregation of ubiquitin and remarkable fragmentation of Golgi complexes prior to neuronal loss. While ubiquitin aggregates and Golgi fragments were accumulating, neurons expressing mutant TDP-43 failed to up-regulate chaperones residing in the endoplasmic reticules and failed to initiate the UPR. Prior to ubiquitin aggregation and Golgi fragmentation, neurons were depleted of X-box-binding protein 1 (XBP1), a key player of UPR machinery. Although it remains to determine how mutation of TDP-43 leads to the failure of the UPR, our data demonstrate that failure of the UPR is implicated in TDP-43 pathogenesis.
    Journal of Neurochemistry 09/2012; 123(3):406-16. DOI:10.1111/jnc.12014 · 4.24 Impact Factor
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