The dynamic nuclear envelope: resilience in health and dysfunction in disease.

The canonical appearance of the nucleus depends on constant adaptation and remodeling of the nuclear envelope in response to changing biomechanical forces and metabolic demands. Dynamic events at the nuclear envelope play a vital role in supporting key nuclear functions as well as conferring plasticity to this organelle. Moreover, imbalance of these dynamic processes is emerging as a central feature of disease etiology. This review focuses on recent advances that shed light on the myriad events at the nuclear envelope that contribute to resilience and flexibility in nuclear architecture.

A role for Nup153 in nuclear assembly reveals differential requirements for targeting of nuclear envelope constituents.

Assembly of the nucleus following mitosis requires rapid and coordinate recruitment of diverse constituents to the inner nuclear membrane. We have identified an unexpected role for the nucleoporin Nup153 in promoting the continued addition of a subset of nuclear envelope (NE) proteins during initial expansion of nascent nuclei. Specifically, disrupting the function of Nup153 interferes with ongoing addition of B-type lamins, lamin B receptor, and SUN1 early in telophase, after the NE has initially enclosed chromatin. In contrast, effects on lamin A and SUN2 were minimal, pointing to differential requirements for the ongoing targeting of NE proteins. Further, distinct mistargeting phenotypes arose among the proteins that require Nup153 for NE targeting. Thus, disrupting the function of Nup153 in nuclear formation reveals several previously undescribed features important for establishing nuclear architecture: 1) a role for a nuclear basket constituent in ongoing recruitment of nuclear envelope components, 2) two functionally separable phases of NE formation in mammalian cells, and 3) distinct requirements of individual NE residents for continued targeting during the expansion phase of NE reformation.