Lumenal interactions in nuclear pore complex assembly and stability

Yewdell, William T.; Colombi, Paolo; Makhnevych, Taras; Lusk, C. Patrick

doi:10.1091/mbc.e10-06-0554

Cited by 57 publications

(76 citation statements)

References 86 publications

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“…Since nups are found in multiple copies in a mature NPC, NPC assembly requires at least 450 nup protomers in yeast (Alber et al, 2007a; 2007b) and many more in human cells (Bui et al, 2013). The spatiotemporal regulation of these events and the biochemical intermediates in this process remain ill defined, although integral INM proteins of the LEM (Lap2-emerin-MAN1)(Yewdell et al, 2011) and SUN (Sad1, UNC84) families (Talamas and Hetzer, 2011) might help form early NPC assembly intermediates.…”

Section: Introductionmentioning

confidence: 99%

Surveillance of Nuclear Pore Complex Assembly by ESCRT-III/Vps4

Webster

Colombi

Jäger

et al. 2014

Cell

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SUMMARY The maintenance of nuclear compartmentalization by the nuclear envelope and nuclear pore complexes (NPCs) is essential for cell function; loss of compartmentalization is associated with cancers, laminopathies and aging. We uncovered a pathway that surveils NPC assembly intermediates to promote the formation of functional NPCs. Surveillance is mediated by Heh2, a member of the LEM (Lap2-emerin-MAN1) family of integral inner nuclear membrane proteins, which binds to an early NPC assembly intermediate, but not to mature NPCs. Heh2 recruits the Endosomal Sorting Complex Required for Transport (ESCRT) – III subunit Snf7 and the AAA-ATPase Vps4 to destabilize and clear defective NPC assembly intermediates. When surveillance or clearance is compromised, malformed NPCs accumulate in a Storage of Improperly assembled Nuclear Pore Complexes compartment, or SINC. The SINC is retained in old mothers to prevent loss of daughter lifespan, highlighting a continuum of mechanisms to ensure nuclear compartmentalization.

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Section: Introductionmentioning

confidence: 99%

Surveillance of Nuclear Pore Complex Assembly by ESCRT-III/Vps4

Webster

Colombi

Jäger

et al. 2014

Cell

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222

328

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“…2, will then drive the shape transformation of the nucleus by overcoming the elevated bending and surface energies stored in the deformed membrane. Recent evidence has indeed shown that various inner nuclear membrane proteins such as Heh1, Heh2, and Ima1 can bind and anchor chromatids to the NE (28)(29)(30)(31). Thus, it is conceivable that such connection prevents chromosomes from sliding away from the nuclear membrane during their contact and ultimately allows the poleward force to be transmitted to the NE.…”

Section: Theoretical Modelmentioning

confidence: 99%

Shape Transformation of the Nuclear Envelope during Closed Mitosis

Zhu

Zheng

Liu

et al. 2016

Biophysical Journal

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The nuclear envelope (NE) in lower eukaryotes such as Schizosaccharomyces pombe undergoes large morphology changes during closed mitosis. However, which physical parameters are important in governing the shape evolution of the NE, and how defects in the dividing chromosomes/microtubules are reflected in those parameters, are fundamental questions that remain unresolved. In this study, we show that improper separation of chromosomes in genetically deficient cells leads to membrane tethering or asymmetric division in contrast to the formation of two equal-sized daughter nuclei in wild-type cells. We hypothesize that the poleward force is transmitted to the nuclear membrane through its physical contact with the separated sister chromatids at the two spindle poles. A theoretical model is developed to predict the morphology evolution of the NE where key factors such as the work done by the poleward force and bending and surface energies stored in the membrane have been taken into account. Interestingly, the predicted phase diagram, summarizing the dependence of nuclear shape on the size of the load transmission regions, and the pole-to-pole distance versus surface area relationship all quantitatively agree well with our experimental observations, suggesting that this model captures the essential physics involved in closed mitosis.

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“…In a surveillance model, Heh2 and/or ESCRT-III would have the capacity to recognize these aberrant assembly intermediates to facilitate their removal. Since Heh2 is capable of binding nups, but is not a stable component of NPCs, 29 we think that it is the most likely candidate that might help biochemically distinguish between an NPC assembly intermediate and an NPC. The mechanism by which Heh2 might perform this function is not obvious, but we favor a model in which there is an upstream factor likely in the ubiquitinproteasome system capable of recognizing and ubiquitylating aberrant NPC assembly intermediates.…”

Section: Escrt-iii Prevents Aberrant Npc Assemblymentioning

confidence: 99%

“…For example, several studies suggest the involvement of integral INM proteins in helping to form an early NPC assembly intermediate. 29,38 Moreover, NLSs are found on nups important for early assembly events. [39][40][41][42] Lastly, biochemical intermediates and invaginations of the INM have been observed after the genetic imposition of assembly blocks.…”

Section: Does Escrt-iii Directly Contribute To Npc Biogenesis?mentioning

confidence: 99%

ESCRTs breach the nuclear border

Webster

Lusk

2015

Nucleus

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T he endosomal sorting complexes required for transport (ESCRT) are best known for their role in sorting ubiquitylated membrane proteins into endosomes. The most ancient component of the ESCRT machinery is ESCRT-III, which is capable of oligomerizing into a helical filament that drives the invagination and scission of membranes aided by the AAA ATPase, Vps4, in several additional subcellular contexts. Our recent study broadens the work of ESCRT-III by identifying its role in a quality control pathway at the nuclear envelope (NE) that ensures the normal biogenesis of nuclear pore complexes (NPCs). Here, we will elaborate on how we envision this mechanism to progress and incorporate ESCRT-III into an emerging model of nuclear pore formation. Moreover, we speculate there are additional roles for the ESCRT-III machinery at the NE that broadly function to ensure its integrity and the maintenance of the nuclear compartment.

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Lumenal interactions in nuclear pore complex assembly and stability

Cited by 57 publications

References 86 publications

Surveillance of Nuclear Pore Complex Assembly by ESCRT-III/Vps4

Surveillance of Nuclear Pore Complex Assembly by ESCRT-III/Vps4

Shape Transformation of the Nuclear Envelope during Closed Mitosis

ESCRTs breach the nuclear border

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