System analysis shows distinct mechanisms and common principles of nuclear envelope protein dynamics

J Cell Biol. 2011 Apr 4;193(1):109-23. doi: 10.1083/jcb.201009068. Epub 2011 Mar 28.

Abstract

The nuclear envelope contains >100 transmembrane proteins that continuously exchange with the endoplasmic reticulum and move within the nuclear membranes. To better understand the organization and dynamics of this system, we compared the trafficking of 15 integral nuclear envelope proteins using FRAP. A surprising 30-fold range of mobilities was observed. The dynamic behavior of several of these proteins was also analyzed after depletion of ATP and/or Ran, two functions implicated in endoplasmic reticulum-inner nuclear membrane translocation. This revealed that ATP- and Ran-dependent translocation mechanisms are distinct and not used by all inner nuclear membrane proteins. The Ran-dependent mechanism requires the phenylalanine-glycine (FG)-nucleoporin Nup35, which is consistent with use of the nuclear pore complex peripheral channels. Intriguingly, the addition of FGs to membrane proteins reduces FRAP recovery times, and this also depends on Nup35. Modeling of three proteins that were unaffected by either ATP or Ran depletion indicates that the wide range in mobilities could be explained by differences in binding affinities in the inner nuclear membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Nucleus / metabolism*
  • Computational Biology
  • Endoplasmic Reticulum / metabolism
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Dynamics Simulation
  • Nuclear Envelope / metabolism*
  • Rats
  • ran GTP-Binding Protein / metabolism

Substances

  • Membrane Proteins
  • Adenosine Triphosphate
  • ran GTP-Binding Protein