Structural Basis of Vesicle Formation at the Inner Nuclear Membrane

Christoph Hagen et al
Cell, Volume 163, Issue 7, p1692–1701, 17 December 2015
DOI: http://dx.doi.org/10.1016/j.cell.2015.11.029

A general cellular mechanism for transportation of large cargoes across the nuclear envelope is vesicular nucleo-cytoplasmic transport.  After recruiting Cargo, it’s enveloped at the inner nuclear membrane (INM), and delivered at the outer nuclear membrane by membrane fusion. The nuclear egress of progeny herpesvirus capsids was investigated to understand the structural underpinning for this trafficking. It was possible to visualize the nuclear egress complex (NEC) in situ forming coated vesicles of defined size by using a multi-modal imaging approach. revealed a protein layer was revealed by cellular electron cryo-tomography showing two distinct hexagonal lattices at its membrane-proximal and membrane-distant faces, respectively. It was possible to determined NEC coat architecture by combining this information with integrative modeling using small-angle X-ray scattering data. The basic mechanism for budding and scission of tailored vesicles at the INM is established by the molecular arrangement of the NEC.

Conclusions: The NEC appears capable of autoscission by continuing assembly of NEC units on the inside of the forming vesicle and requires no external energy input for both membrane budding and scission. Moreover, the characterization of the viral cargo packing system at the INM opens the search for the respective cellular counterparts and molecular determinants mediating nuclear egress of large cargo, including ribonucleoprotein particles.

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http://dx.doi.org/10.1016/j.cell.2015.11.029