Components of an ESCRT-independent nuclear envelope assembly pathway

Abstract

Following chromosome segregation, the nuclear envelope (NE) must be reassembled and holes in the nuclear membrane must be “sealed.” During NE assembly, the NE-specific adaptor, Cmp7, recruits and activates ESCRT-III proteins to mediate NE sealing. However, recent evidence suggests the presence of alternative mechanisms. In a screen using the fission yeast, S. japonicus, we recently implicated the ESCRT adaptor, Alx1, and a conserved, but little studied protein, Vid27, in Cmp7-independent NE assembly. Here, we provide direct evidence that Alx1 functions in a Cmp7- and ESCRT-independent NE assembly pathway via positive regulation of Vid27. Consistent with a role in membrane remodeling, Vid27 localizes to sites of postmitotic NE sealing and is essential in S. japonicus. Alx1 and Vid27 form a complex and mutations disrupting their interaction abolish Alx1’s enhancement of Vid27 function at the NE. Further, we find that Bqt4 and the Lem2-Nur1 complex, which function in tethering heterochromatin to the NE and modulating NE lipid composition, bind Vid27. Vid27 contains a canonical Bqt4-binding motif and likely interacts directly with Bqt4, indicating that Vid27 could plausibly work with Bqt4 in its NE assembly function. Together, these findings define components of a new Cmp7- and ESCRT-independent NE assembly pathway, advancing our understanding of the mechanisms crucial for maintaining nuclear integrity.