The integrity of the nuclear envelope barrier relies on membrane remodeling by the ESCRTs, which seal nuclear envelope holes and contribute to the quality control of nuclear pore complexes (NPCs); whether these processes are mechanistically related remains poorly defined. Here, we show that the ESCRT‐II/III chimera, Chm7, is recruited to a nuclear envelope subdomain that expands upon inhibition of NPC assembly and is required for the formation of the storage of improperly assembled NPCs (SINC) compartment. Recruitment to sites of NPC assembly is mediated by its ESCRT‐II domain and the LAP2‐emerin‐MAN1 (LEM) family of integral inner nuclear membrane proteins, Heh1 and Heh2. We establish direct binding between Heh2 and the “open” forms of both Chm7 and the ESCRT‐III, Snf7, and between Chm7 and Snf7. Interestingly, Chm7 is required for the viability of yeast strains where double membrane seals have been observed over defective NPCs; deletion of CHM7 in these strains leads to a loss of nuclear compartmentalization suggesting that the sealing of defective NPCs and nuclear envelope ruptures could proceed through similar mechanisms.
ESCRT protein Chm7 acts with integral inner nuclear membrane proteins Heh1 and Heh2 at sites of nuclear pore complex (NPC) assembly to seal off defective NPCs, thereby protecting nuclear compartmentalization and cell viability.
The orphan ESCRT Chm7 is recruited to the nuclear envelope by its ESCRT‐II‐like N‐terminal domain and direct binding to conserved integral membrane proteins of the LAP2‐emerin‐MAN1 (LEM) family.
Chm7 is enriched at the nuclear envelope when NPC assembly is blocked.
Deleterious gain of function of Chm7 causes the accumulation of newly synthesized nucleoporins in the storage of improperly assembled nuclear pore complexes (SINC) compartment.
CHM7 is required for the viability and nuclear compartmentalization of yeast strains where double‐membrane seals are observed over defective nuclear pore complexes.
The EMBO Journal (2016) 35: 2447–2467
- Received April 17, 2016.
- Revision received September 21, 2016.
- Accepted September 22, 2016.
- © 2016 The Authors