An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity

Abstract

The molecular mechanisms by which the endosomal sorting complexes required for transport (ESCRT) proteins contribute to the integrity of the nuclear envelope (NE) barrier are not fully defined. Here, we leveraged the single NE hole generated by mitotic extrusion of the Schizosaccharomyces pombe spindle pole body (SPB) to reveal two modes of ESCRT function executed by distinct complements of ESCRT-III proteins, both depending on CHMP7/Cmp7. A grommet-like function is required to restrict the NE hole in anaphase B, while replacement of Cmp7 by a sealing module ultimately closes the NE in interphase. Without Cmp7, nucleocytoplasmic compartmentalization surprisingly remains intact despite NE discontinuities up to 550 nm, suggesting mechanisms to prevent diffusion through these holes. We implicate SPB proteins as key components of a diffusion barrier acting with Cmp7 in anaphase B. Thus, NE remodeling mechanisms cooperate with proteinaceous diffusion barriers beyond nuclear pore complexes to protect the nuclear compartment.