Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus

Dorsch, Anna D; Hölper, Julia E.; Franzke, Kati; Zaeck, Luca M.; Mettenleiter, Thomas C.; Klupp, Barbara G.

doi:10.3390/v13061117

Cited by 3 publications

(3 citation statements)

References 63 publications

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“…Similar observations were made in cells overexpressing Nup107 or lamin B, which enforced a chromosome separation checkpoint to prevent NE reformation on incompletely separated chromosomes (Afonso et al, 2014). Clearly, a function of VAPB in mitosis is not essential, as VAPB-knockout cells (Dorsch et al, 2021) as well as knockout mice (Silbernagel et al, 2018) are viable. One cellular component that could function here as a rescue factor is VAPA, a protein very similar in sequence and localization to VAPB (Lev et al, 2008).…”

Section: Similar Effects Have Been Observed Upon Knock Down Of Severa...mentioning

confidence: 68%

Phosphorylation-dependent interactions of VAPB and ELYS contribute to the temporal progression of mitosis

Kehlenbach

James

Möller

et al. 2023

Preprint

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ELYS is a nucleoporin that localizes to the nuclear side of the nuclear envelope in interphase cells. In mitosis, it serves as an assembly platform that interacts with chromatin and then with nucleoporin subcomplexes to initiate the formation of novel nuclear pore complexes. Here we describe the interaction of ELYS with the membrane protein VAPB. In mitosis, ELYS becomes phosphorylated at many sites, including a predicted FFAT (two phenylalanines in an acidic tract) motif, which is shown to mediate interaction with the MSP (major sperm protein)-domain of VAPB. Phosphorylation-dependent binding of VAPB to ELYS is demonstrated by peptide binding assays and co-immunoprecipitation experiments. In anaphase, the two proteins co-localize to the non-core region of the newly forming nuclear envelope. Depletion of VAPB resulted in prolonged mitosis and slow progression from meta- to anaphase and also to chromosome segregation defects. Together, our results suggest an active role of VAPB in recruiting membrane fragments to chromatin and in the biogenesis of a novel nuclear envelope during mitosis.

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Section: Similar Effects Have Been Observed Upon Knock Down Of Severa...mentioning

confidence: 68%

Phosphorylation-dependent interactions of VAPB and ELYS contribute to the temporal progression of mitosis

Kehlenbach

James

Möller

et al. 2023

Preprint

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“…Knockdown of VAPB caused accumulations of PEVs (129). In contrast, cells deficient for VAPA and/or VAPB did not show any impact on nuclear egress or formation of infectious progeny of PrV (130).…”

Section: Role Of Vesicle-associated Membrane-associated Proteinsmentioning

confidence: 81%

The Knowns and Unknowns of Herpesvirus Nuclear Egress

Klupp

Mettenleiter

2023

Annu. Rev. Virol.

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Nuclear egress of herpesvirus capsids across the intact nuclear envelope is an exceptional vesicle-mediated nucleocytoplasmic translocation resulting in the delivery of mature herpesvirus capsids into the cytosol. Budding of the (nucleo)capsid at and scission from the inner nuclear membrane (INM) is mediated by the dimeric viral nuclear egress complex (NEC) resulting in a transiently enveloped virus particle in the perinuclear space followed by fusion of the primary envelope with the outer nuclear membrane (ONM). The NEC oligomerizes into a honeycomb-shaped coat underlining the INM to induce membrane curvature and scission. Mutational analyses complemented structural data defining functionally important regions. Questions remain, including where and when the NEC is formed and how membrane curvature is mediated, vesicle formation is regulated, and directionality is secured. The composition of the primary enveloped virion and the machinery mediating fusion of the primary envelope with the ONM is still debated. While NEC-mediated budding apparently follows a highly conserved mechanism, species and/or cell type–specific differences complicate understanding of later steps. Expected final online publication date for the Annual Review of Virology, Volume 10 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Similar observations were made in cells overexpressing Nup107 or lamin B, which enforced a chromosome separation checkpoint to prevent NE reformation on incompletely separated chromosomes (Afonso et al, 2014 ). Clearly, a function of VAPB in mitosis is not essential, as VAPB-knockout cells (Dorsch et al, 2021 ) as well as knockout mice (Silbernagel et al, 2018 ) are viable. Other cellular components that could function here as rescue factors are VAPA, a paralog very similar in sequence and localization to VAPB (Lev et al, 2008 ), and MOSPD2 (Di Mattia et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of ELYS promotes its interaction with VAPB at decondensing chromosomes during mitosis

James,

Möller,

Spillner

et al. 2024

EMBO Rep

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ELYS is a nucleoporin that localizes to the nuclear side of the nuclear pore complex (NPC) in interphase cells. In mitosis, it serves as an assembly platform that interacts with chromatin and then with nucleoporin subcomplexes to initiate post-mitotic NPC assembly. Here we identify ELYS as a major binding partner of the membrane protein VAPB during mitosis. In mitosis, ELYS becomes phosphorylated at many sites, including a predicted FFAT (two phenylalanines in an acidic tract) motif, which mediates interaction with the MSP (major sperm protein)-domain of VAPB. Binding assays using recombinant proteins or cell lysates and co-immunoprecipitation experiments show that VAPB binds the FFAT motif of ELYS in a phosphorylation-dependent manner. In anaphase, the two proteins co-localize to the non-core region of the newly forming nuclear envelope. Depletion of VAPB results in prolonged mitosis, slow progression from meta- to anaphase and in chromosome segregation defects. Together, our results suggest a role of VAPB in mitosis upon recruitment to or release from ELYS at the non-core region of the chromatin in a phosphorylation-dependent manner.

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Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus

Cited by 3 publications

References 63 publications

Phosphorylation-dependent interactions of VAPB and ELYS contribute to the temporal progression of mitosis

Phosphorylation-dependent interactions of VAPB and ELYS contribute to the temporal progression of mitosis

The Knowns and Unknowns of Herpesvirus Nuclear Egress

Phosphorylation of ELYS promotes its interaction with VAPB at decondensing chromosomes during mitosis

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