Molecular basis for sculpting the endoplasmic reticulum membrane

Lin, Shao-Yu; Sun, Sha; Hu, Junjie

doi:10.1016/j.biocel.2012.05.013

Cited by 47 publications

(50 citation statements)

References 71 publications

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“…Result in ER Expansion-The ER is highly dynamic, and its morphology is tightly regulated (10,11). Abnormal ER morphology is associated with hereditary spastic paraplegias and related disorders (38).…”

Section: Losses Of Sec22 and Syx5mentioning

confidence: 99%

Sec22 Regulates Endoplasmic Reticulum Morphology but Not Autophagy and Is Required for Eye Development in Drosophila

Zhao¹,

Yang

Liu³

et al. 2015

Journal of Biological Chemistry

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Background: ER morphological changes are often observed in disease conditions, but the molecular mechanisms remain unclear. Results: Malfunction of Sec22 and its binding partners resulted in ER expansion and defects in fly eye development. Conclusion: Sec22 regulates ER morphology through regulating ER-Golgi trafficking but not autophagy. Significance: ER morphology changes under the disease conditions might be due to the defects of ER-Golgi trafficking.

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Section: Losses Of Sec22 and Syx5mentioning

confidence: 99%

Sec22 Regulates Endoplasmic Reticulum Morphology but Not Autophagy and Is Required for Eye Development in Drosophila

Zhao¹,

Yang

Liu³

et al. 2015

Journal of Biological Chemistry

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“…The morphology of these regions is maintained by the microtubule network, as well as by ER-associated proteins such as Climp-63, Dp1, reticulon family members, and reticulon-like proteins, which are evolutionarily conserved from yeast to humans (44)(45)(46)(47)(48). The sheet structure is collaboratively maintained by Climp-63 and the reticulons, while the peripheral tubules require tubulin with support from the reticulons (49). The reticulon (Rtn) family members include a number of genes and splice variants, with most mammalian cells having some combination of the splice variants of Rtn4/Nogo (referred to as Rtn4a/ Nogo-A, Rtn4b/Nogo-B1, and Rtn 4d/Nogo-B2) (48).…”

mentioning

confidence: 99%

Endoplasmic Reticulum Tubule Protein Reticulon 4 Associates with the Legionella pneumophila Vacuole and with Translocated Substrate Ceg9

et al. 2015

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Intracellular growth of Legionella pneumophila occurs in a replication vacuole constructed by host proteins that regulate vesicular traffic from the host endoplasmic reticulum (ER). This process is promoted by a combination of approximately 300 Icm/Dot translocated substrates (IDTS). One of these proteins, Ceg9, was previously identified in a screen for L. pneumophila IDTS that manipulate secretory traffic when overexpressed in yeast. Using ectopic expression of Ceg9 in mammalian cells, we demonstrate that Ceg9 interacts with isoforms of host reticulon 4 (Rtn4), a protein that regulates ER tubule formation. Binding occurs under conditions that prevent association with other known reticulon binding proteins, arguing that Ceg9 binding is stable. A tripartite complex was demonstrated among Rtn4, Ceg9, and atlastin 1, a previously characterized reticulon interacting partner. The binding of Ceg9 to Rtn4 was not due to bridging by atlastin 1 but resulted from the two interacting partners binding independently to reticulon. When Ceg9 is ectopically expressed in mammalian cells, it shows a localization pattern that is indistinguishable from that of Rtn4, perhaps due to interactions between and similar structural features of the two proteins. Consistent with Rtn4 playing a role in the formation of the Legionella-containing vacuole, it was recruited to almost 50% of the vacuoles within 20 min postinfection. Our studies suggest that L. pneumophila proteins interact with ER tubules at an early stage of replication vacuole formation. I ntravacuolar growth of intracellular pathogens involves intimate interaction with specific subsets of host cell membrane compartments (1). In the case of Chlamydia trachomatis, the association of the replication vacuole with the trans-Golgi and the endoplasmic reticulum (ER) network is a key step during the establishment of an intracellular niche (2-5). Similarly, vacuoles harboring Brucella, Salmonella, and Mycobacterium species also interface with defined membrane compartments that aid the growth of these bacteria in host cells (6-10). Failure to establish association with the appropriate organelles can have dire consequences, including loss of vacuolar membrane integrity, activation of inflammatory host cell death, and trafficking of the microorganism into degradative compartments (3,6,11,12).Legionella pneumophila is one such intravacuolar pathogen that targets specific intracellular compartments during its replication cycle (13-16). The bacterium is a pathogen of amoebae and humans. In humans, L. pneumophila's primary manifestation of virulence is Legionnaires' disease, a potentially lethal pneumonia resulting from growth of the bacteria within alveolar macrophages (17, 18). Biogenesis of the microbial replication vacuole is evolutionarily conserved from amoebae to eukaryotic cells (16,19), with the bacterium growing in an ER-encompassed compartment called the Legionella-containing vacuole (LCV) (13,15,20). The connection between the LCV and ER dynamics is well established, since the prop...

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“…Among them, ER membrane-bound GTPases, animal atlastins and yeast Sey1p (Synthetic Enhancement of Yop1), function as ER fusogens to form the interconnected tubular network (Hu et al, 2009;Orso et al, 2009;Anwar et al, 2012). Atlastin molecules on the two opposed membranes have been proposed to transiently dimerize to attract the two membranes to each other (Bian et al, 2011;Byrnes and Sondermann, 2011;MorinLeisk et al, 2011;Moss et al, 2011;Lin et al, 2012;Byrnes et al, 2013). Closely attracted lipid bilayers are supposed to be destabilized by an amphipathic helical domain at the atlastin C terminus to facilitate membrane fusion (Bian et al, 2011;Liu et al, 2012;Faust et al, 2015).…”

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confidence: 99%

Phosphorylation of the C Terminus of RHD3 Has a Critical Role in Homotypic ER Membrane Fusion in Arabidopsis

et al. 2015

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The endoplasmic reticulum (ER) consists of dynamically changing tubules and cisternae. In animals and yeast, homotypic ER membrane fusion is mediated by fusogens (atlastin and Sey1p, respectively) that are membrane-associated dynamin-like GTPases. In Arabidopsis (Arabidopsis thaliana), another dynamin-like GTPase, ROOT HAIR DEFECTIVE3 (RHD3), has been proposed as an ER membrane fusogen, but direct evidence is lacking. Here, we show that RHD3 has an ER membrane fusion activity that is enhanced by phosphorylation of its C terminus. The ER network was RHD3-dependently reconstituted from the cytosol and microsome fraction of tobacco (Nicotiana tabacum) cultured cells by exogenously adding GTP, ATP, and F-actin. We next established an in vitro assay system of ER tubule formation with Arabidopsis ER vesicles, in which addition of GTP caused ER sac formation from the ER vesicles. Subsequent application of a shearing force to this system triggered the formation of tubules from the ER sacs in an RHD-dependent manner. Unexpectedly, in the absence of a shearing force, Ser/Thr kinase treatment triggered RHD3-dependent tubule formation. Mass spectrometry showed that RHD3 was phosphorylated at multiple Ser and Thr residues in the C terminus. An antibody against the RHD3 C-terminal peptide abolished kinase-triggered tubule formation. When the Ser cluster was deleted or when the Ser residues were replaced with Ala residues, kinase treatment had no effect on tubule formation. Kinase treatment induced the oligomerization of RHD3. Neither phosphorylation-dependent modulation of membrane fusion nor oligomerization has been reported for atlastin or Sey1p. Taken together, we propose that phosphorylation-stimulated oligomerization of RHD3 enhances ER membrane fusion to form the ER network.

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Molecular basis for sculpting the endoplasmic reticulum membrane

Cited by 47 publications

References 71 publications

Sec22 Regulates Endoplasmic Reticulum Morphology but Not Autophagy and Is Required for Eye Development in Drosophila

Sec22 Regulates Endoplasmic Reticulum Morphology but Not Autophagy and Is Required for Eye Development in Drosophila

Endoplasmic Reticulum Tubule Protein Reticulon 4 Associates with the Legionella pneumophila Vacuole and with Translocated Substrate Ceg9

Phosphorylation of the C Terminus of RHD3 Has a Critical Role in Homotypic ER Membrane Fusion in Arabidopsis

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