Balancing ER dynamics: shaping, bending, severing, and mending membranes

Pendin, Diana; McNew, James A.; Daga, Andrea

doi:10.1016/j.ceb.2011.04.007

Cited by 57 publications

(41 citation statements)

References 53 publications

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“…33,34) RBs are thought to be membrane-bound structures derived from the ER, where misfolded proteins are accumulating. [7][8][9] However, dynamics of RB and association of RB with other organelles are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Russell Bodies Accumulating Mutant Antithrombin Derived from the Endoplasmic Reticulum

Kimura

Kawaguchi

Ueda

et al. 2015

Biological & Pharmaceutical Bulletin

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The endoplasmic reticulum (ER) adjusts its size and architecture to adapt to change in the surrounding environment. Russell bodies (RBs) were originally described as dilated structures of the ER cisternae containing large amounts of mutant immunoglobulin. Similar structures are observed in a wide variety of mutant proteins accumulated in the ER. We previously prepared Chinese hamster ovary (CHO) cells in which the expression of mutant antithrombin (AT) (C95R) was controlled with a Tet-On system and showed that RBs can be conditionally formed. However the precise architecture and intracellular behavior of RBs have been as yet only poorly characterized. To characterize the properties of RB, we prepared the same system using a green fluorescent protein (GFP)-fused mutant and measured the dynamics and architecture of RBs. We observed the mobile nature of the molecule in the RB lumen and RBs were separated from the rest of the ER network by narrow tubes. Furthermore, we found that the RBs were not simply expanded ER membranes. The RB lumen is filled with misfolded proteins that are surrounded by ER membranes. In addition, RBs mostly maintain their structure during cell division, possess ribosomes on their membranes and synthesize AT(C95R)-GFP. Based on the characterization of the hydrodynamic radius of AT(C95R)-GFP and the effect of DP1, an ER-shaping protein, we propose that RBs are spontaneously formed as a result of the partitioning of the misfolded AT with the shaping protein.

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Section: Discussionmentioning

confidence: 99%

Characterization of Russell Bodies Accumulating Mutant Antithrombin Derived from the Endoplasmic Reticulum

Kimura

Kawaguchi

Ueda

et al. 2015

Biological & Pharmaceutical Bulletin

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“…The endoplasmic reticulum (ER) is a continuous membrane structure composed of sheet-like cisternae and a polygonal array of tubules connected by three-way junctions (Baumann and Walz, 2001;English et al, 2009;Shibata et al, 2009;Pendin et al, 2011). The ER structure is highly dynamic; new membrane tubules are continuously formed and fused with other tubules to form three-way junctions (Lee and Chen, 1988).…”

Section: Introductionmentioning

confidence: 99%

Contribution of the long form of syntaxin 5 to the organization of the endoplasmic reticulum

Miyazaki

Wakana

Noda

et al. 2012

Journal of Cell Science

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SummaryThe SNARE protein syntaxin 5 exists as long (42 kDa) and short (35 kDa) isoforms. The short form is principally localized in the Golgi complex, whereas the long form resides not only in the Golgi but also in the endoplasmic reticulum (ER). Although the Golgi-localized short form has been extensively investigated, little is known about the long form. In the present study, we demonstrate that the long form of syntaxin 5 functions to shape the ER. We found that overexpression of the long form of syntaxin 5 induces rearrangement and coalignment of the ER membrane with microtubules, the pattern of which is quite similar to that observed in cells overexpressing CLIMP-63, a linker between the ER membrane and microtubules. The ability of syntaxin 5 to induce ER-microtubule rearrangement is not related to its SNARE function, but correlates with its binding affinities for CLIMP-63, and CLIMP-63 is essential for the induction of this rearrangement. Microtubule co-sedimentation assays demonstrated that the long form of syntaxin 5 has a substantial microtubulebinding activity. These results suggest that the long form of syntaxin 5 contributes to the regulation of ER structure by interacting with both CLIMP-63 and microtubules. Indeed, depletion of syntaxin 5 caused the spreading of the ER to the cell periphery, similar to the phenotype observed in cells treated with the microtubule-depolymerizing reagent nocodazole. Our results disclose a previously undescribed function of the long form of syntaxin 5 that is not related to its function as a SNARE.

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“…This interconnected nature of the ER network is required for ER function and is maintained by the ER membrane fusion GTPase atlastin (Orso et al, 2009), which is a member of the fusion dynamin-related protein family (fusion DRP) (McNew et al, 2013;Moss et al, 2011;Pendin et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

Summerville

Faust

Fan

et al. 2016

Journal of Cell Science

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108

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Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-type Drosophila motor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 ortholog atl. atl or Rtnl1 loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss of atl causes age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior.

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Balancing ER dynamics: shaping, bending, severing, and mending membranes

Cited by 57 publications

References 53 publications

Characterization of Russell Bodies Accumulating Mutant Antithrombin Derived from the Endoplasmic Reticulum

Characterization of Russell Bodies Accumulating Mutant Antithrombin Derived from the Endoplasmic Reticulum

Contribution of the long form of syntaxin 5 to the organization of the endoplasmic reticulum

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

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