Wash and the wash regulatory complex function in nuclear envelope budding

Abstract

Nuclear envelope budding is a recently described phenomenon wherein large macromolecular complexes are packaged inside the nucleus and extruded through the nuclear membranes. While a general outline of the cellular events occurring during NE-budding is now in place, little is yet known about the molecular machinery and mechanisms underlying the physical aspects of NE-bud formation. Using a multidisciplinary approach, we identify Wash, its regulatory complex (SHRC), capping protein, and Arp2/3 as new molecular components involved in the physical aspects of NE-bud formation. Interestingly, Wash affects NE-budding in two ways: indirectly through general nuclear lamina disruption via an SHRC-independent interaction with Lamin B leading to inefficient NE-bud formation, and directly blocking NE-bud formation along with its SHRC, capping protein, and Arp2/3. In addition to NE-budding emerging as an important cellular process, it shares many similarities with herpesvirus nuclear egress mechanisms suggesting new avenues for exploration in both normal and disease biology.