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Discovering how inner nuclear membrane protein, LEM2, orchestrates timely nuclear envelope reformation during open mitosis


Membranes are fundamental to cellular life. They define the cellular border and establish biochemically specialized subcellular compartments. As cell grow, change, and divide, cellular membranes are remodeled accordingly: undergoing membrane fission and fusion to maintain cellular architecture. For example, the nuclear membrane that organizes and protects DNA is remodeled during cell division. In cells that undergo “open mitosis”, the nuclear membrane is fully disassembled to allow chromosomes to be segregated by the spindle apparatus and reassembled following chromosome segregation. Understanding how cells remodel nuclear membranes to rebuild nuclei with every cell division is critical to understanding the core principals of membrane biology that underlie cellular life.

In my dissertation, I describe how a membrane fusion complex is organized to seal holes in the reforming nuclear envelope that are occupied by spindle microtubules. Using biochemical approaches, I find that an inner nuclear membrane protein, called LEM2, uses multivalent, low-affinity binding interactions to condense in a liquid-like phase at the junction of the nuclear envelope, chromatin, and residual spindle microtubules. There, LEM2 activates the ESCRT protein, CHMP7, in a looping copolymer. Together, the fluid LEM2 toroid and structured LEM2-CHMP7 copolymer collaborate to serve as a molecular “O-ring” for early nuclear sealing. Furthermore, the LEM2-CHMP7 ring serves as a foundation for the membrane-remodeling ESCRT-III complex to execute coupled spindle disassembly and membrane fusion. This work establishes a new paradigm in membrane organization, in which a liquid-like protein phase can function as both a barrier within a discontinuous membrane and a scaffold for membrane fusion factors.

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