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Visualizing nuclear pore complex plasticity with pan-expansion microscopy.

Kimberly J Morgan¹, Emma Carley¹, Alyssa N Coyne^2,3

¹Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.

The Journal of Cell Biology

|June 12, 2025

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New tools reveal nuclear pore complex (NPC) plasticity. LINC complexes influence NPC diameter by affecting nuclear envelope tension, and POM121 localization changes in disease.

Area of Science:

Cell Biology
Biophysics

Background:

Investigating nuclear pore complex (NPC) plasticity in response to cell type and environment is crucial.
Accessible tools are needed to study NPC size and localization dynamics.

Purpose of the Study:

To develop and utilize novel methods for visualizing and quantifying NPC plasticity.
To understand the role of LINC complexes and nuclear envelope tension in regulating NPC diameter.
To examine NPC structural changes in disease models.

Main Methods:

Pan-expansion microscopy (pan-ExM) for high-resolution imaging of NPCs.
Machine learning-based segmentation for NPC identification and analysis.
Experimental manipulations including hyperosmotic shock and LINC complex depletion.

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Main Results:

NPCs display a wide range of diameters, with dilation biased towards the basal nuclear surface.
Hyperosmotic shock causes NPC constriction, while LINC complex depletion removes basal dilation bias.
POM121 relocalizes within NPCs in patient-derived neurons with C9orf72 amyotrophic lateral sclerosis.

Conclusions:

Pan-expansion microscopy is effective for studying NPC plasticity at single-NPC resolution.
LINC complexes may modulate local nuclear envelope tension to regulate NPC dilation.
NPC structural alterations, like POM121 shift, are observable in disease contexts.