Structural Basis of Vesicle Formation at the Inner Nuclear Membrane

Christoph Hagen; Kyle C. Dent; Tzviya Zeev-Ben-Mordehai; Michael Grange; Jens B. Bosse; Cathy Whittle; Barbara G. Klupp; C. Alistair Siebert; Daven Vasishtan; Felix J.B. Bäuerlein; Juliana Cheleski; Stephan Werner; Peter Guttmann; Stefan Rehbein; Katja Henzler; Justin Demmerle; Barbara Adler; Ulrich Koszinowski; Lothar Schermelleh; Gerd Schneider; Lynn W. Enquist; Jürgen M. Plitzko; Thomas C. Mettenleiter; Kay Grünewald

doi:10.1016/j.cell.2015.11.029

Structural Basis of Vesicle Formation at the Inner Nuclear Membrane

Christoph Hagen, Kyle C. Dent, Tzviya Zeev-Ben-Mordehai, Michael Grange, Jens B. Bosse, Cathy Whittle, Barbara G. Klupp, C. Alistair Siebert, Daven Vasishtan, Felix J.B. Bäuerlein, Juliana Cheleski, Stephan Werner, Peter Guttmann, Stefan Rehbein, Katja Henzler, Justin Demmerle, Barbara Adler, Ulrich Koszinowski, Lothar Schermelleh, Gerd SchneiderLynn W. Enquist, Jürgen M. Plitzko, Thomas C. Mettenleiter, Kay Grünewald

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140 Scopus citations

Abstract

Vesicular nucleo-cytoplasmic transport is becoming recognized as a general cellular mechanism for translocation of large cargoes across the nuclear envelope. Cargo is recruited, enveloped at the inner nuclear membrane (INM), and delivered by membrane fusion at the outer nuclear membrane. To understand the structural underpinning for this trafficking, we investigated nuclear egress of progeny herpesvirus capsids where capsid envelopment is mediated by two viral proteins, forming the nuclear egress complex (NEC). Using a multi-modal imaging approach, we visualized the NEC in situ forming coated vesicles of defined size. Cellular electron cryo-tomography revealed a protein layer showing two distinct hexagonal lattices at its membrane-proximal and membrane-distant faces, respectively. NEC coat architecture was determined by combining this information with integrative modeling using small-angle X-ray scattering data. The molecular arrangement of the NEC establishes the basic mechanism for budding and scission of tailored vesicles at the INM.

Original language	English (US)
Pages (from-to)	1692-1701
Number of pages	10
Journal	Cell
Volume	163
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2015.11.029
State	Published - Dec 17 2015

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2015.11.029

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Hagen, C., Dent, K. C., Zeev-Ben-Mordehai, T., Grange, M., Bosse, J. B., Whittle, C., Klupp, B. G., Siebert, C. A., Vasishtan, D., Bäuerlein, F. J. B., Cheleski, J., Werner, S., Guttmann, P., Rehbein, S., Henzler, K., Demmerle, J., Adler, B., Koszinowski, U., Schermelleh, L., ... Grünewald, K. (2015). Structural Basis of Vesicle Formation at the Inner Nuclear Membrane. Cell, 163(7), 1692-1701. https://doi.org/10.1016/j.cell.2015.11.029

@article{511438340a6740c18c5496be9613be4f,

title = "Structural Basis of Vesicle Formation at the Inner Nuclear Membrane",

abstract = "Vesicular nucleo-cytoplasmic transport is becoming recognized as a general cellular mechanism for translocation of large cargoes across the nuclear envelope. Cargo is recruited, enveloped at the inner nuclear membrane (INM), and delivered by membrane fusion at the outer nuclear membrane. To understand the structural underpinning for this trafficking, we investigated nuclear egress of progeny herpesvirus capsids where capsid envelopment is mediated by two viral proteins, forming the nuclear egress complex (NEC). Using a multi-modal imaging approach, we visualized the NEC in situ forming coated vesicles of defined size. Cellular electron cryo-tomography revealed a protein layer showing two distinct hexagonal lattices at its membrane-proximal and membrane-distant faces, respectively. NEC coat architecture was determined by combining this information with integrative modeling using small-angle X-ray scattering data. The molecular arrangement of the NEC establishes the basic mechanism for budding and scission of tailored vesicles at the INM.",

author = "Christoph Hagen and Dent, {Kyle C.} and Tzviya Zeev-Ben-Mordehai and Michael Grange and Bosse, {Jens B.} and Cathy Whittle and Klupp, {Barbara G.} and Siebert, {C. Alistair} and Daven Vasishtan and B{\"a}uerlein, {Felix J.B.} and Juliana Cheleski and Stephan Werner and Peter Guttmann and Stefan Rehbein and Katja Henzler and Justin Demmerle and Barbara Adler and Ulrich Koszinowski and Lothar Schermelleh and Gerd Schneider and Enquist, {Lynn W.} and Plitzko, {J{\"u}rgen M.} and Mettenleiter, {Thomas C.} and Kay Gr{\"u}newald",

note = "Funding Information: We thank Wolfram Antonin (T{\"u}bingen) for critical discussion and Marion Jasnin, Tim Laugks, Miroslava Schaffer, and Margarete Sch{\"u}ler for help with cryoFIB in Martinsried. This work was supported by a Wellcome Trust Senior Research Fellowship to K.G. (090895/Z/09/Z), German Research Council grants DFG GR1990/2 to K.G. and DFG Me 854/12-1 to T.C.M., a Leverhulme Trust grant to K.G. (RPG-2012-519), a Wellcome Trust JIF award (060208/Z/00/Z) and a Wellcome Trust equipment grant (093305/Z/10/Z) to the Oxford Particle Imaging Centre, the Wellcome Trust core award 090532/Z/09/Z to the Wellcome Trust Centre for Human Genetics, the Wellcome Trust Strategic Award 091911 supporting advanced microscopy at Micron Oxford, a Wellcome Trust PhD studentship to M.G., a S{\~a}o Paulo Research Foundation Fellowship to J.C. (Fapesp 2013/24972-1), and a DFG Fellowship BO 4158/1-1 to J.B.B. We acknowledge the Helmholtz-Zentrum Berlin electron storage ring BESSY II for provision of synchrotron radiation at beamline U41-FSGM. The research leading to these results has received funding from the European Community{\textquoteright}s Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (Grant agreement nos. 283570 and 226716). Publisher Copyright: {\textcopyright} 2015 The Authors.",

year = "2015",

month = dec,

day = "17",

doi = "10.1016/j.cell.2015.11.029",

language = "English (US)",

volume = "163",

pages = "1692--1701",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "7",

}

Hagen, C, Dent, KC, Zeev-Ben-Mordehai, T, Grange, M, Bosse, JB, Whittle, C, Klupp, BG, Siebert, CA, Vasishtan, D, Bäuerlein, FJB, Cheleski, J, Werner, S, Guttmann, P, Rehbein, S, Henzler, K, Demmerle, J, Adler, B, Koszinowski, U, Schermelleh, L, Schneider, G, Enquist, LW, Plitzko, JM, Mettenleiter, TC & Grünewald, K 2015, 'Structural Basis of Vesicle Formation at the Inner Nuclear Membrane', Cell, vol. 163, no. 7, pp. 1692-1701. https://doi.org/10.1016/j.cell.2015.11.029

TY - JOUR

T1 - Structural Basis of Vesicle Formation at the Inner Nuclear Membrane

AU - Hagen, Christoph

AU - Dent, Kyle C.

AU - Zeev-Ben-Mordehai, Tzviya

AU - Grange, Michael

AU - Bosse, Jens B.

AU - Whittle, Cathy

AU - Klupp, Barbara G.

AU - Siebert, C. Alistair

AU - Vasishtan, Daven

AU - Bäuerlein, Felix J.B.

AU - Cheleski, Juliana

AU - Werner, Stephan

AU - Guttmann, Peter

AU - Rehbein, Stefan

AU - Henzler, Katja

AU - Demmerle, Justin

AU - Adler, Barbara

AU - Koszinowski, Ulrich

AU - Schermelleh, Lothar

AU - Schneider, Gerd

AU - Enquist, Lynn W.

AU - Plitzko, Jürgen M.

AU - Mettenleiter, Thomas C.

AU - Grünewald, Kay

N1 - Funding Information: We thank Wolfram Antonin (Tübingen) for critical discussion and Marion Jasnin, Tim Laugks, Miroslava Schaffer, and Margarete Schüler for help with cryoFIB in Martinsried. This work was supported by a Wellcome Trust Senior Research Fellowship to K.G. (090895/Z/09/Z), German Research Council grants DFG GR1990/2 to K.G. and DFG Me 854/12-1 to T.C.M., a Leverhulme Trust grant to K.G. (RPG-2012-519), a Wellcome Trust JIF award (060208/Z/00/Z) and a Wellcome Trust equipment grant (093305/Z/10/Z) to the Oxford Particle Imaging Centre, the Wellcome Trust core award 090532/Z/09/Z to the Wellcome Trust Centre for Human Genetics, the Wellcome Trust Strategic Award 091911 supporting advanced microscopy at Micron Oxford, a Wellcome Trust PhD studentship to M.G., a São Paulo Research Foundation Fellowship to J.C. (Fapesp 2013/24972-1), and a DFG Fellowship BO 4158/1-1 to J.B.B. We acknowledge the Helmholtz-Zentrum Berlin electron storage ring BESSY II for provision of synchrotron radiation at beamline U41-FSGM. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (Grant agreement nos. 283570 and 226716). Publisher Copyright: © 2015 The Authors.

PY - 2015/12/17

Y1 - 2015/12/17

N2 - Vesicular nucleo-cytoplasmic transport is becoming recognized as a general cellular mechanism for translocation of large cargoes across the nuclear envelope. Cargo is recruited, enveloped at the inner nuclear membrane (INM), and delivered by membrane fusion at the outer nuclear membrane. To understand the structural underpinning for this trafficking, we investigated nuclear egress of progeny herpesvirus capsids where capsid envelopment is mediated by two viral proteins, forming the nuclear egress complex (NEC). Using a multi-modal imaging approach, we visualized the NEC in situ forming coated vesicles of defined size. Cellular electron cryo-tomography revealed a protein layer showing two distinct hexagonal lattices at its membrane-proximal and membrane-distant faces, respectively. NEC coat architecture was determined by combining this information with integrative modeling using small-angle X-ray scattering data. The molecular arrangement of the NEC establishes the basic mechanism for budding and scission of tailored vesicles at the INM.

AB - Vesicular nucleo-cytoplasmic transport is becoming recognized as a general cellular mechanism for translocation of large cargoes across the nuclear envelope. Cargo is recruited, enveloped at the inner nuclear membrane (INM), and delivered by membrane fusion at the outer nuclear membrane. To understand the structural underpinning for this trafficking, we investigated nuclear egress of progeny herpesvirus capsids where capsid envelopment is mediated by two viral proteins, forming the nuclear egress complex (NEC). Using a multi-modal imaging approach, we visualized the NEC in situ forming coated vesicles of defined size. Cellular electron cryo-tomography revealed a protein layer showing two distinct hexagonal lattices at its membrane-proximal and membrane-distant faces, respectively. NEC coat architecture was determined by combining this information with integrative modeling using small-angle X-ray scattering data. The molecular arrangement of the NEC establishes the basic mechanism for budding and scission of tailored vesicles at the INM.

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UR - http://www.scopus.com/inward/citedby.url?scp=84950262686&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2015.11.029

DO - 10.1016/j.cell.2015.11.029

M3 - Article

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AN - SCOPUS:84950262686

SN - 0092-8674

VL - 163

SP - 1692

EP - 1701

JO - Cell

JF - Cell

IS - 7

ER -

Structural Basis of Vesicle Formation at the Inner Nuclear Membrane

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