The nucleus – arguably the cell's most important organelle – is anything but simple. In addition to housing DNA and all of its associated protein machinery, the nucleus also contains an extensive network of structural proteins. One of these is called protein 4.1R, which was first described as an essential mediator of erythrocyte shape and mechanical stability. Protein 4.1R has since also been described in nucleated cells, where it is crucial for the assembly and maintenance of functional nuclei. 4.1R acts as a linker protein that interacts with diverse binding partners. But which interactions are key to its roles in regulating nuclear structure and function? On page , Sharon Wald Krauss and colleagues now provide an answer to this question by showing that 4.1R associates with the nuclear envelope protein emerin and the intermediate filament protein lamin A/C. Furthermore, depletion of 4.1R perturbs lamin A networks, emerin localisation and the distribution of other nuclear proteins. These changes impact upon nuclear morphology, and the distance between the centrosome and the nuclear envelope, and cause an increase in nuclear β-catenin transcriptional activity. In mice, the partial knockdown of 4.1R results in disease phenotypes, such as cardiac and kidney defects and neurobehavioural deficits. Thus, 4.1R is clearly a key player that links nuclear and cytoplasmic structures to maintain nuclear shape and function.
