ESCRTs breach the nuclear border

Abstract

T he endosomal sorting complexes required for transport (ESCRT) are best known for their role in sorting ubiquitylated membrane proteins into endosomes. The most ancient component of the ESCRT machinery is ESCRT-III, which is capable of oligomerizing into a helical filament that drives the invagination and scission of membranes aided by the AAA ATPase, Vps4, in several additional subcellular contexts. Our recent study broadens the work of ESCRT-III by identifying its role in a quality control pathway at the nuclear envelope (NE) that ensures the normal biogenesis of nuclear pore complexes (NPCs). Here, we will elaborate on how we envision this mechanism to progress and incorporate ESCRT-III into an emerging model of nuclear pore formation. Moreover, we speculate there are additional roles for the ESCRT-III machinery at the NE that broadly function to ensure its integrity and the maintenance of the nuclear compartment.

Consequences of a tight squeeze: Nuclear envelope rupture and repair

“…[26][27][28] The ESCRT machinery was originally described as a vacuole-sorting complex, 29 and subsequently recognized to mediate many additional cellular processes, such as plasma membrane repair, cytokinetic abscission, viral budding at the plasma membrane, endocytosis and secretion, and NPC insertion into the NE. [30][31][32] In all of these processes, the ESCRT machinery mediates the membrane remodeling by promoting membrane curvature and, in most cases, driving membrane scission. The ESCRT machinery consists of multiple subunits, ranging from ESCRT-0 to ESCRT-III.…”

Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing

“…While no single dedicated membrane bending or fusion machinery has been identified that drives nuclear pore formation, an emerging theme is the cooperative action of nups containing amphipathic helices or reticulon domains capable of recognizing and/or generating membrane curvature (Marelli et al, 2001;Drin et al, 2007;Dawson et al, 2009;Chadrin et al, 2010;Doucet et al, 2010;Vollmer et al, 2012Vollmer et al, , 2015von Appen et al, 2015;Casey et al, 2015;Floch et al, 2015;Mészáros et al, 2015). Interestingly, budding yeast requires the membrane bending and scission endosomal sorting complexes required for transport (ESCRT)-III proteins to ensure formation of functional NPCs, raising the possibility that an established multifunctional membrane remodeler that acts during pore biogenesis may yet be identified (Webster et al, 2014;Webster & Lusk, 2015). Consistent with this idea, genetic ablation of ESCRT-III components and the AAA-ATPase Vps4 leads to the accumulation of defective NPCs in a compartment called the storage of improperly assembled NPCs compartment (SINC), which is subsequently retained in mother cells (Webster et al, 2014).…”

Border Safety: Quality Control at the Nuclear Envelope

“…1B). Last, an exciting possibility would invoke a model in which ESCRTs clear misassembled nups through a vesicular intermediate within the NE lumen[62](Fig. 1B) in a mechanism analogous to herpesvirus nuclear egress[63].…”