Assembly of nuclear pore complexes mediated by major vault protein

Vollmar, Friederike; Hacker, Christian; Zahedi, René P.; Sickmann, Albert; Ewald, Andrea; Scheer, Ulrich; Dabauvalle, Marie-Christine

doi:10.1242/jcs.039529

Cited by 22 publications

(19 citation statements)

References 36 publications

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“…In addition, several vault specific RNAs (vRNAs) are found. The function or functions of vaults are still unclear; they are associated with drug resistance and several signalling pathways (reviewed in [102]), as well as the nuclear pore complex [103,104]. vPARP-deficient mice are normal and fertile with no defects in telomeres or vaults [105].…”

Section: Discussionmentioning

confidence: 99%

Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes

2010

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BackgroundThe Poly(ADP-ribose)polymerase (PARP) superfamily was originally identified as enzymes that catalyze the attachment of ADP-ribose subunits to target proteins using NAD+ as a substrate. The family is characterized by the catalytic site, termed the PARP signature. While these proteins can be found in a range of eukaryotes, they have been best studied in mammals. In these organisms, PARPs have key functions in DNA repair, genome integrity and epigenetic regulation. More recently it has been found that proteins within the PARP superfamily have altered catalytic sites, and have mono(ADP-ribose) transferase (mART) activity or are enzymatically inactive. These findings suggest that the PARP signature has a broader range of functions that initially predicted. In this study, we investigate the evolutionary history of PARP genes across the eukaryotes.ResultsWe identified in silico 236 PARP proteins from 77 species across five of the six eukaryotic supergroups. We performed extensive phylogenetic analyses of the identified PARPs. They are found in all eukaryotic supergroups for which sequence is available, but some individual lineages within supergroups have independently lost these genes. The PARP superfamily can be subdivided into six clades. Two of these clades were likely found in the last common eukaryotic ancestor. In addition, we have identified PARPs in organisms in which they have not previously been described.ConclusionsThree main conclusions can be drawn from our study. First, the broad distribution and pattern of representation of PARP genes indicates that the ancestor of all extant eukaryotes encoded proteins of this type. Second, the ancestral PARP proteins had different functions and activities. One of these proteins was similar to human PARP1 and likely functioned in DNA damage response. The second of the ancestral PARPs had already evolved differences in its catalytic domain that suggest that these proteins may not have possessed poly(ADP-ribosyl)ation activity. Third, the diversity of the PARP superfamily is larger than previously documented, suggesting as more eukaryotic genomes become available, this gene family will grow in both number and type.

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Section: Discussionmentioning

confidence: 99%

Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes

2010

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“…These experimental conditions serve as a model for the interphase mode of assembly in metazoan cells (D'Angelo et al, 2006;Doucet et al, 2010;Harel et al, 2003a;Vollmar et al, 2009). When POM121 DN is added to a pre-formed NE, NPC insertion does occur, but it is uncoupled from nuclear membrane expansion.…”

Section: Discussionmentioning

confidence: 99%

“…Cell-free systems derived from amphibian egg extracts have long served as an experimental model to study postmitotic NPC assembly (Antonin et al, 2005;Forbes et al, 1983;Harel et al, 2003b;Lohka and Masui, 1983;Rotem et al, 2009;Walther et al, 2003) and can also be used to follow NPC insertion into intact membranes (D'Angelo et al, 2006;Harel et al, 2003a;Vollmar et al, 2009). To test for a potential dominant-negative effect in the nuclear reconstitution assay, we expressed several fragments of Xenopus laevis POM121, lacking the transmembrane segment, as recombinant GST fusion proteins in bacteria (supplementary material Fig.…”

Section: A Dose-dependent Inhibitory Effect Of a Soluble Pom121 Fragmentmentioning

confidence: 99%

A dominant-negative form of POM121 binds chromatin and disrupts the two separate modes of nuclear pore assembly

Shaulov

Gruber

Cohen

et al. 2011

Journal of Cell Science

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SummaryNuclear pore complexes (NPCs) are formed during two separate stages of the metazoan cell cycle. They are assembled into the reforming nuclear envelope (NE) at the exit from mitosis and into an intact, expanding NE during interphase. Here, we show that a soluble internal fragment of the membrane nucleoporin POM121 has a dominant-negative effect on both modes of assembly in a cell-free reconstitution system. The soluble POM121 fragment binds chromatin at sites that are distinct from ELYS-Nup107-160 'seeding' sites and prevents membrane enclosure and NPC formation. Importin-b negatively regulates chromatin binding by the POM121 fragment through a conserved NLS motif and is also shown to affect the recruitment of the endogenous membrane protein to chromatin in the full assembly system. When an intact NE is present before the addition of the dominant-negative fragment, NPCs are inserted into the NE but membrane expansion is inhibited. This results in densely packed NPCs with no intervening membrane patches, as visualized by scanning electron microscopy. We conclude that POM121 plays an important role in both modes of assembly and links nuclear membrane formation and expansion to nuclear pore biogenesis.

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“…The widely used Xenopus egg extracts system, which formally recapitulates post-mitotic NE and NPC formation, was adapted by several groups to study insertion of pores in an intact NE. Indeed, pore-free NEs can be assembled using the calcium-chelator BAPTA (Doucet et al 2010;Harel et al 2003a, b) or subfractionated membranes (Vollmar et al 2009), and can be used to study subsequent pore assembly into intact NEs. Interphase pore assembly can also be studied during the expansion phase of in vitro assembled nuclei (D'Angelo et al 2006;Doucet et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Nuclear pore biogenesis into an intact nuclear envelope

Doucet

Hetzer

2010

Chromosoma

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Nuclear pore complexes (NPCs) serve as transport channels across the nuclear membrane, a double lipid bilayer that physically separates the nucleoplasm and cytoplasm of eukaryotic cells. New evidence suggests that the multiprotein nuclear pores also play a role in chromatin organization and gene expression. Given the importance of NPC function, it is not surprising that a growing list of human diseases and developmental defects have been linked to its malfunction. In order to fully understand the functional repertoire of NPCs and their essential role for nuclear organization, it is critical to determine the sequence of events that lead to the formation of nuclear pores. This is particularly relevant since NPC number, and possibly composition, are tightly linked to metabolic activity. Most of our knowledge is derived from NPC formation that occurs in dividing cells at the end of mitosis when the nuclear envelope (NE) and NPCs reform from disassembled precursors. However, NPC assembly also takes place during interphase into an intact NE. Importantly, this process is not restricted to dividing cells but also occurs during cell differentiation. Here, we will review aspects unique to this process, namely the regulation of nuclear expansion and the mechanisms of fusion between the outer and inner nuclear membranes. We will then discuss conserved and diverging mechanisms between post-mitotic and interphase assembly of the proteinaceous structure in light of recently published data.

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Assembly of nuclear pore complexes mediated by major vault protein

Cited by 22 publications

References 36 publications

Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes

Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes

A dominant-negative form of POM121 binds chromatin and disrupts the two separate modes of nuclear pore assembly

Nuclear pore biogenesis into an intact nuclear envelope

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