Nucleocytoplasmic transport rates are regulated by cellular processes that modulate GTP availability

J Cell Biol. 2024 Jul 1;223(7):e202308152. doi: 10.1083/jcb.202308152. Epub 2024 Apr 29.

Abstract

Nucleocytoplasmic transport (NCT), the facilitated diffusion of cargo molecules between the nucleus and cytoplasm through nuclear pore complexes (NPCs), enables numerous fundamental eukaryotic cellular processes. Ran GTPase uses cellular energy in the direct form of GTP to create a gradient across the nuclear envelope (NE) that drives the majority of NCT. We report here that changes in GTP availability resulting from altered cellular physiology modulate the rate of NCT, as monitored using synthetic and natural cargo, and the dynamics of Ran itself. Cell migration, cell spreading, and/or modulation of the cytoskeleton or its connection to the nucleus alter GTP availability and thus rates of NCT, regulating RNA export and protein synthesis. These findings support a model in which changes in cellular physiology that alter GTP availability can regulate the rate of NCT, impacting fundamental cellular processes that extensively utilize NCT.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus*
  • Animals
  • Cell Movement
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Cytoskeleton / metabolism
  • Guanosine Triphosphate* / metabolism
  • Humans
  • Nuclear Envelope / metabolism
  • Nuclear Pore / genetics
  • Nuclear Pore / metabolism
  • Protein Biosynthesis
  • ran GTP-Binding Protein* / genetics
  • ran GTP-Binding Protein* / metabolism

Substances

  • Guanosine Triphosphate
  • ran GTP-Binding Protein