Efficient protein targeting to the inner nuclear membrane requires Atlastin-dependent maintenance of ER topology

Elife. 2017 Aug 14:6:e28202. doi: 10.7554/eLife.28202.


Newly synthesized membrane proteins are targeted to the inner nuclear membrane (INM) by diffusion within the membrane system of the endoplasmic reticulum (ER), translocation through nuclear pore complexes (NPCs) and retention on nuclear partners. Using a visual in vitro assay we previously showed that efficient protein targeting to the INM depends on nucleotide hydrolysis. We now reveal that INM targeting is GTP-dependent. Exploiting in vitro reconstitution and in vivo analysis of INM targeting, we establish that Atlastins, membrane-bound GTPases of the ER, sustain the efficient targeting of proteins to the INM by their continued activity in preserving ER topology. When ER topology is altered, the long-range diffusional exchange of proteins in the ER network and targeting efficiency to the INM are diminished. Highlighting the general importance of proper ER topology, we show that Atlastins also influence NPC biogenesis and timely exit of secretory cargo from the ER.

Keywords: ER; GTPase; atlastin; biochemistry; cell biology; human; inner nuclear membrane; membrane protein; nuclear envelope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • GTP-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Nuclear Envelope / metabolism*
  • Protein Binding
  • Protein Transport


  • Membrane Proteins
  • ATL1 protein, human
  • GTP-Binding Proteins

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.