Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4

Cell. 2014 Oct 9;159(2):388-401. doi: 10.1016/j.cell.2014.09.012.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Adenosine Triphosphatases / metabolism*
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Nuclear Pore / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism*


  • Endosomal Sorting Complexes Required for Transport
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • VPS4 protein, S cerevisiae
  • Vps4 protein, S pombe
  • Adenosine Triphosphatases