Reciprocal regulation between lunapark and atlastin facilitates ER three-way junction formation

Zhou, Xin; He, Yu; Huang, Xiaofang; Guo, Yuting; Liu, Dong; Hu, Junjie

doi:10.1007/s13238-018-0595-7

Cited by 27 publications

(21 citation statements)

References 42 publications

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“…membranes at these regions become less deformable. In addition, Lnp inhibits ATL-mediated membrane fusion (Zhou et al, 2018). A mechanism in which Lnp counteracts ATL is consistent with the observations that overexpression of Lnp in mammalian tissue culture cells leads to expanded junctional sheets with ATL located at the edges and that co-overexpression of ATL restores a normal ER network (Wang et al, 2016).…”

Section: Reconstitution Of Lnp and Its Implicationssupporting

confidence: 86%

“…However, although Lnp localizes preferentially to three-way junctions of the ER, it is not essential for their formation. Indeed, mammalian cells lacking Lnp have more ER sheets, but the tubular network does not completely disappear, particularly remaining at the periphery of the cells (Wang et al, 2016;Zhou et al, 2018).…”

Section: Reconstitution Of Lnp and Its Implicationsmentioning

confidence: 99%

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Reconstituting the reticular ER network – mechanistic implications and open questions

Wang

Rapoport

2019

Journal of Cell Science

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The endoplasmic reticulum (ER) is a major membrane-bound organelle in all eukaryotic cells. This organelle comprises morphologically distinct domains, including the nuclear envelope and peripheral sheets and tubules. The tubules are connected by three-way junctions into a network. Several membrane proteins have been implicated in network formation; curvature-stabilizing proteins generate the tubules themselves, and membrane-anchored GTPases fuse tubules into a network. Recent experiments have shown that a tubular network can be formed with reconstituted proteoliposomes containing the yeast membrane-fusing GTPase Sey1 and a curvature-stabilizing protein of either the reticulon or REEP protein families. The network forms in the presence of GTP and is rapidly disassembled when GTP hydrolysis of Sey1 is inhibited, indicating that continuous membrane fusion is required for its maintenance. Atlastin, the ortholog of Sey1 in metazoans, forms a network on its own, serving both as a fusion and curvature-stabilizing protein. These results show that the reticular ER can be generated by a surprisingly small set of proteins, and represents an energydependent steady state between formation and disassembly. Models for the molecular mechanism by which curvature-stabilizing proteins cooperate with fusion GTPases to form a reticular network have been proposed, but many aspects remain speculative, including the function of additional proteins, such as the lunapark protein, and the mechanism by which the ER interacts with the cytoskeleton. How the nuclear envelope and peripheral ER sheets are formed remain major unresolved questions in the field. Here, we review reconstitution experiments with purified curvature-stabilizing proteins and fusion GTPases, discuss mechanistic implications and point out open questions.

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Section: Reconstitution Of Lnp and Its Implicationssupporting

confidence: 86%

Section: Reconstitution Of Lnp and Its Implicationsmentioning

confidence: 99%

Reconstituting the reticular ER network – mechanistic implications and open questions

Wang

Rapoport

2019

Journal of Cell Science

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“…In the tubular ER, a protein family named lunapark (Lnp) localizes at the three-way junctions. The N-terminal domain of Lnp contains an N-myristoylation site and a coiled-coil 1 domain (CC1) which is predicted to form an amphipathic helix (Zhou et al, 2019). The hydrophobic surface of the CC1 in the N-terminal domain of Lnp binds junction-enriched atlastins for proper localization and this interaction compromises atlastin-mediated membrane fusion (Zhou et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…The N-terminal domain of Lnp contains an N-myristoylation site and a coiled-coil 1 domain (CC1) which is predicted to form an amphipathic helix (Zhou et al, 2019). The hydrophobic surface of the CC1 in the N-terminal domain of Lnp binds junction-enriched atlastins for proper localization and this interaction compromises atlastin-mediated membrane fusion (Zhou et al, 2019). It would be interesting to test whether hydrophobic surface of the amphipathic helix of Arfrp1 and Arl14 interact with specific cellular factors and analyze the functional roles of these interactions.…”

Section: Discussionmentioning

confidence: 99%

The amphipathic helices of Arfrp1 and Arl14 are sufficient to determine subcellular localizations

Yang

Peng

et al. 2020

Journal of Biological Chemistry

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The subcellular localization of Arf family proteins is generally thought to be determined by their corresponding guanine nucleotide exchange factors (GEFs). By promoting GTP binding, GEFs induce conformational changes of Arf proteins exposing their N-terminal amphipathic helices, which then insert into the membranes to stabilize the membrane association process. Here, we found the N-terminal amphipathic motifs of the Golgi-localized Arf family protein, Arfrp1, and the endosome- and plasma membrane-localized Arf family protein, Arl14, play critical roles in spatial determination. Exchanging the amphipathic helix motifs between these two Arf proteins causes the switch of their localizations. Moreover, the amphipathic helices of Arfrp1 and Arl14 are sufficient for cytosolic proteins to be localized into a specific cellular compartment. The spatial determination mediated by the Arfrp1 helix requires its binding partner Sys1. In addition, the residues that are required for the acetylation of the Arfrp1 helix and the myristoylation of the Arl14 helix are important for the specific subcellular localization. Interestingly, Arfrp1 and Arl14 are recruited to their specific cellular compartments independent of GTP binding. Our results demonstrate that the amphipathic motifs of Arfrp1 and Arl14 are sufficient for determining specific subcellular localizations in a GTP-independent manner, suggesting the membrane association and activation of some Arf proteins are uncoupled.

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“…This protein is directly involved in shaping the ER tubular network by stabilizing three-way junctions between ER tubules, where it also localizes (Chen et al, 2012(Chen et al, , 2015. Absence of Lunapark in mammalian cells increases the amount of ER sheets, but does not abolish the formation of an ER tubular network (Wang S. et al, 2016;Zhou et al, 2018), suggesting that although required to stabilize the three-way junctions, Lunapark is not essential to develop ER tubules.…”

Section: Axonal Er Organizationmentioning

confidence: 99%

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

2020

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The physical continuity of axons over long cellular distances poses challenges for their maintenance. One organelle that faces this challenge is endoplasmic reticulum (ER); unlike other intracellular organelles, this forms a physically continuous network throughout the cell, with a single membrane and a single lumen. In axons, ER is mainly smooth, forming a tubular network with occasional sheets or cisternae and low amounts of rough ER. It has many potential roles: lipid biosynthesis, glucose homeostasis, a Ca 2+ store, protein export, and contacting and regulating other organelles. This tubular network structure is determined by ER-shaping proteins, mutations in some of which are causative for neurodegenerative disorders such as hereditary spastic paraplegia (HSP). While axonal ER shares many features with the tubular ER network in other contexts, these features must be adapted to the long and narrow dimensions of axons. ER appears to be physically continuous throughout axons, over distances that are enormous on a subcellular scale. It is therefore a potential channel for long-distance or regional communication within neurons, independent of action potentials or physical transport of cargos, but involving its physiological roles such as Ca 2+ or organelle homeostasis. Despite its apparent stability, axonal ER is highly dynamic, showing features like anterograde and retrograde transport, potentially reflecting continuous fusion and breakage of the network. Here we discuss the transport processes that must contribute to this dynamic behavior of ER. We also discuss the model that these processes underpin a homeostatic process that ensures both enough ER to maintain continuity of the network and repair breaks in it, but not too much ER that might disrupt local cellular physiology. Finally, we discuss how failure of ER organization in axons could lead to axon degenerative diseases, and how a requirement for ER continuity could make distal axons most susceptible to degeneration in conditions that disrupt ER continuity.

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Reciprocal regulation between lunapark and atlastin facilitates ER three-way junction formation

Cited by 27 publications

References 42 publications

Reconstituting the reticular ER network – mechanistic implications and open questions

Reconstituting the reticular ER network – mechanistic implications and open questions

The amphipathic helices of Arfrp1 and Arl14 are sufficient to determine subcellular localizations

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

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