title: Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4.
abstract: The maintenance of nuclear compartmentalization by the nuclear envelope and nuclear pore complexes (NPCs) is essential for cell function; loss of compartmentalization is associated with cancers, laminopathies, and aging. We uncovered a pathway that surveils NPC assembly intermediates to promote the formation of functional NPCs. Surveillance is mediated by Heh2, a member of the LEM (Lap2-emerin-MAN1) family of integral inner nuclear membrane proteins, which binds to an early NPC assembly intermediate, but not to mature NPCs. Heh2 recruits the endosomal sorting complex required for transport (ESCRT)-III subunit Snf7 and the AAA-ATPase Vps4 to destabilize and clear defective NPC assembly intermediates. When surveillance or clearance is compromised, malformed NPCs accumulate in a storage of improperly assembled nuclear pore complexes compartment, or SINC. The SINC is retained in old mothers to prevent loss of daughter lifespan, highlighting a continuum of mechanisms to ensure nuclear compartmentalization.
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Brant M
authors.initials: BM
authors.lastname: Webster
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombi
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Jäger
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: patrick.lusk@yale.edu.
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Lusk
mesh_terms: D021581:Active Transport, Cell Nucleus; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D022022:Nuclear Pore / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C107528:VPS4 protein, S cerevisiae; C000595805:Vps4 protein, S pombe; D000251:Adenosine Triphosphatases