Quality control of NPC assembly
The NPC imposes a barrier to movement of macromolecules across the nuclear envelope – this compartmentalization is essential for normal cell function. Indeed, disruption of nuclear compartmentalization is associated with various diseases including cancers and “laminopathies”. Moroever, recent work supports that the loss of the function of the NPC-diffusion barrier might contribute to the appearance of protein aggregates in the nucleus of old neurons – a hallmark of neurodegeneration. We have identified a surveillance mechanism
that ensures proper NPC assembly by clearing and degrading defective NPC assembly intermediates. Moreover, in a asymmetric division model like budding yeast, we have also explored mechanisms that both retain defective NPCs in mothers and promote the passage of functional NPCs to daughters thus ensuring daughter lifespan.