Integrating complex functions: coordination of nuclear pore complex assembly and membrane expansion of the nuclear envelope requires a family of integral membrane proteins

Nucleus. Sep-Oct 2010;1(5):387-92. doi: 10.4161/nucl.1.5.12333.


The nuclear envelope harbors numerous large proteinaceous channels, the nuclear pore complexes (NPCs), through which macromolecular exchange between the cytosol and the nucleoplasm occurs. This double-membrane nuclear envelope is continuous with the endoplasmic reticulum and thus functionally connected to such diverse processes as vesicular transport, protein maturation and lipid synthesis. Recent results obtained from studies in Saccharomyces cerevisiae indicate that assembly of the nuclear pore complex is functionally dependent upon maintenance of lipid homeostasis of the ER membrane. Previous work from one of our laboratories has revealed that an integral membrane protein Apq12 is important for the assembly of functional nuclear pores. Cells lacking APQ12 are viable but cannot grow at low temperatures, have aberrant NPCs and a defect in mRNA export. Remarkably, these defects in NPC assembly can be overcome by supplementing cells with a membrane fluidizing agent, benzyl alcohol, suggesting that Apq12 impacts the flexibility of the nuclear membrane, possibly by adjusting its lipid composition when cells are shifted to a reduced temperature. Our new study now expands these findings and reveals that an essential membrane protein, Brr6, shares at least partially overlapping functions with Apq12 and is also required for assembly of functional NPCs. A third nuclear envelope membrane protein, Brl1, is related to Brr6, and is also required for NPC assembly. Because maintenance of membrane homeostasis is essential for cellular survival, the fact that these three proteins are conserved in fungi that undergo closed mitoses, but are not found in metazoans or plants, may indicate that their functions are performed by proteins unrelated at the primary sequence level to Brr6, Brl1 and Apq12 in cells that disassemble their nuclear envelopes during mitosis.

Keywords: endoplasmic reticulum; lipid metabolism; membrane homeostasis; nuclear pore complex; nucleocytoplasmic transport; nucleoporins.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Adaptation, Physiological
  • Benzyl Alcohol / pharmacology
  • Cold Temperature
  • Cytoplasm / metabolism
  • Endoplasmic Reticulum / physiology
  • Lipid Metabolism
  • Membrane Fluidity / drug effects
  • Membrane Lipids / physiology
  • Membrane Proteins / metabolism*
  • Mitosis / physiology
  • Nuclear Pore / physiology*
  • Nuclear Proteins / metabolism*
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Apq12 protein, S cerevisiae
  • Brr6 protein, S cerevisiae
  • Membrane Lipids
  • Membrane Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Benzyl Alcohol