Nuclear envelope budding and its cellular functions

Abstract

The nuclear pore complex (NPC) has long been assumed to be the sole route across the nuclear envelope, and under normal homeostatic conditions it is indeed the main mechanism of nucleo-cytoplasmic transport. However, it has also been known that e.g. herpesviruses cross the nuclear envelope utilizing a pathway entitled nuclear egress or envelopment/de-envelopment. Despite this, a thread of observations suggests that mechanisms similar to viral egress may be transiently used also in healthy cells. It has since been proposed that mechanisms like nuclear envelope budding (NEB) can facilitate the transport of RNA granules, aggregated proteins, inner nuclear membrane proteins, and mis-assembled NPCs. Herein, we will summarize the known roles of NEB as a physiological and intrinsic cellular feature and highlight the many unanswered questions surrounding these intriguing nuclear events.

Keywords: Nuclear import; nuclear envelope budding; nuclear export.

Figure 1.

A selection of NEB events from different species found in literature over the past 70 years. a) Electron micrograph of a fruit fly cell [21]. b) Rat oocytes 54,000x magnification [10]. c) Microspores from an Easter lily. 23,000x [20]. d) Drosophila larval muscle nuclei with arrowheads pointing to inner nuclear membrane (INM) and outer nuclear membrane (ONM) [28]. e) Sea urchin gastrula [13]. f) Slice from an electron tomogram of a NEB event in budding yeast. g) Thin section of a fission yeast cell [27]. Scale bars in panels a, d, and e are 500 nm and in panels f and g are 100 nm, scale bars were unavailable in the original publications of panels b and c; N: nucleus, C: cytosol. Arrows are pointing to nuclear budding events, other labels from the original publications were hidden (grey and black dots) to ease comprehension of the adapted figure. (h) Phylogenetic tree of species in which NEB and NEB-like mechanisms has been observed, adapted from [27].

Figure 2.

Scheme of herpesviral egress. Three main steps during the envelopment/de-envelopment process of Herpesviridae are depicted. NEC: nuclear egress complex, PKC: protein kinase C.

Figure 3.

The nature of NEB cargo. Schemes of four modes of nuclear envelope budding events with known cargos and regulators. Panel b shows two modes: (Mode a) Double-membrane vesicle carrying cargo after budding event; (Mode b) Cargo released without membrane enclosure. Organisms, where these modes of actions were described are panel a: Drosophila melanogaster; panels b, c, d (right): Saccharomyces cerevisiae; panel d (left): Mammals. NPC: Nuclear pore complex, PKC: Protein Kinase C.