Alternative nuclear transport for cellular protein quality control - PubMed (original) (raw)

Alternative nuclear transport for cellular protein quality control

April Rose et al. Trends Cell Biol. 2012 Oct.

Abstract

Herpesvirus capsids traverse the nuclear envelope (NE) by utilizing an unusual export pathway termed nuclear egress. In this process, the viral capsid is delivered into the perinuclear space (PNS), producing a vesicular intermediate after fission. After fusion with the outer nuclear membrane (ONM), the naked capsid is released into the cytosol. A recent study now suggests that this pathway might be an endogenous cellular pathway, co-opted by viruses, that serves to transport cellular cargo exceeding the size limit imposed by the nuclear pore complex (NPC). We propose that one function of this pathway is to transport nuclear protein aggregates to the cytosolic autophagy machinery. Our model has implications for our understanding of laminopathies and related diseases affecting proteins residing at the inner nuclear membrane (INM) and nuclear lamina.

Copyright © 2012 Elsevier Ltd. All rights reserved.

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Figures

Figure 1

Figure 1

Egress of herpesvirus capsids from the nucleus: A paradigm for the delivery of nuclear protein aggregates to the cytosolic autophagy machinery? (a). Herpesvirus capsids are assembled in the nucleus and bud into the perinuclear space to form a membrane-enveloped intermediate, which then fuses with the outer nuclear membrane (ONM) to release the naked capsid into the cytosol, where the glycoprotein coat is acquired. (b). Using the same route, nuclear aggregates may be transported to the autophagic machinery that is confined to the cytosol (note that secondary envelopment, depicted in a, is topologically equivalent to isolation membrane formation at the onset of autophagy, depicted in b). The link to autophagy is at present hypothetical and awaits experimental validation (see main text and Box 1).

Figure 2

Figure 2

Manipulation of the nuclear envelope during viral egress. Dissolution of the nuclear lamina by local phosphorylation of nuclear lamins via kinases (i) enables the capsid to gain access to the inner nuclear membrane, and to dock onto the nuclear egress complex (ii). Budding (iii) and fission (iv) produce a vesicular intermediate, which fuses the outer nuclear membrane in a reaction that may involve gB (v). Lmn, Lamins; LBR, Lamin B receptor; PKC, protein kinase C; gB, Glycoprotein B. Cellular proteins are depicted in blue, viral proteins in red/orange. Note that the capsid is not drawn to scale: its diameter is approximately three times the width of the perinuclear space (PNS).

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