The nucleus does not float freely within the cell. Instead it appears to be anchored by complexes that link the cytoskeleton with the nuclear matrix. The nature of these complexes, and how they bridge the inner (INM) and outer nuclear membrane (ONM), is unclear. Padmakumar and co-workers have therefore examined the connections made by the ONM protein nesprin 2 – one of a family of giant actin-binding proteins that may link organelles to cytoskeletal filaments (see ). They use two-hybrid studies to show that the lumenal region of nesprin 2 interacts with Sun1, a potential lamina-associated protein that genetic approaches have implicated in nuclear anchorage. The authors define the regions of the proteins involved and demonstrate that the interaction with Sun1 is critical for correct localization of nesprin 2. Importantly, they also establish that Sun1 resides in the INM – again defining the targeting sequences responsible. Their findings indicate the nesprin-2–Sun1 interaction connects cytoplasmic actin filaments with the nuclear skeleton and thus significantly extend our understanding of how the nucleus is integrated into cellular architecture.
