Visualizing nuclear pore complex plasticity with pan-expansion microscopy.

Journal: The Journal of cell biology
Published Date:

Abstract

The exploration of cell-type and environmentally responsive nuclear pore complex (NPC) plasticity requires new, accessible tools. Using pan-expansion microscopy (pan-ExM), NPCs were identified by machine learning-facilitated segmentation. They exhibited a large range of diameters with a bias for dilated NPCs at the basal nuclear surface in clusters suggestive of local islands of nuclear envelope tension. Whereas hyperosmotic shock constricted NPCs analogously to those found in annulate lamellae, depletion of LINC complexes specifically eliminated the modest nuclear surface diameter biases. Therefore, LINC complexes may contribute locally to nuclear envelope tension to toggle NPC diameter between dilated, but not constricted, states. Lastly, POM121 shifts from the nuclear ring to the inner ring of the NPC specifically in induced pluripotent stem cell-derived neurons from a patient with C9orf72 amyotrophic lateral sclerosis. Thus, pan-ExM is a powerful tool to visualize NPC plasticity in physiological and pathological contexts at single NPC resolution.

Authors

  • Kimberly J Morgan
    Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
  • Emma Carley
    Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
  • Alyssa N Coyne
    Brain Science Institute, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
  • Jeffrey D Rothstein
    Brain Science Institute, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
  • C Patrick Lusk
    Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
  • Megan C King
    Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.