New Insights into Mechanisms and Functions of Nuclear Size Regulation

Nuclear size is generally maintained within a defined range in a given cell type. Changes in cell size that occur during cell growth, development, and differentiation are accompanied by dynamic nuclear size adjustments in order to establish appropriate nuclear-to-cytoplasmic volume relationships. It has long been recognized that aberrations in nuclear size are associated with certain disease states, most notably cancer. Nuclear size and morphology must impact nuclear and cellular functions. Understanding these functional implications requires an understanding of the mechanisms that control nuclear size. In this review, we first provide a general overview of the diverse cellular structures and activities that contribute to nuclear size control, including structural components of the nucleus, effects of DNA amount and chromatin compaction, signaling, and transport pathways that impinge on the nucleus, extranuclear structures, and cell cycle state. We then detail some of the key mechanistic findings about nuclear size regulation that have been gleaned from a variety of model organisms. Lastly, we review studies that have implicated nuclear size in the regulation of cell and nuclear function and speculate on the potential functional significance of nuclear size in chromatin organization, gene expression, nuclear mechanics, and disease. With many fundamental cell biological questions remaining to be answered, the field of nuclear size regulation is still wide open.