title: Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing.
abstract: 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.
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Brant M
authors.initials: BM
authors.lastname: Webster
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Thaller
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Jäger
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ochmann
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Sapan
authors.initials: S
authors.lastname: Borah
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA patrick.lusk@yale.edu.
authors.forename: C Patrick
authors.identifier: 0000-0003-4703-0533
authors.initials: CP
authors.lastname: Lusk
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D022022:Nuclear Pore / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000610602:Chm7 protein, S cerevisiae; D008565:Membrane Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C532133:Src1 protein, S cerevisiae
keywords: 
  ESCRT
  ; LEM domain; nuclear envelope; nuclear transport; quality control