Shaping the nucleus: factors and forces

Abstract

Take a look at a textbook illustration of a cell and you will immediately be able to locate the nucleus, which is often drawn as a spherical or ovoid shaped structure. But not all cells have such nuclei. In fact, some disease states are diagnosed by the presence of nuclei that have an abnormal shape or size. What defines nuclear shape and nuclear size, and how does nuclear geometry affect nuclear function? While the answer to the latter question remains largely unknown, significant progress has been made towards understanding the former. In this review, we provide an overview of the factors and forces that affect nuclear shape and size, discuss the relationship between ER structure and nuclear morphology, and speculate on the possible connection between nuclear size and its shape. We also note the many interesting questions that remain to be explored.

Fig. 1

The nuclear envelope. a: The nuclear envelope (NE) is composed of an outer nuclear membrane (ONM) and an inner nuclear membrane (INM), which meet at sites where nuclear pore complexes (NPCs, in orange, see panel b for details) are embedded. The ONM is continuous with the ER membrane, and the lumen between the ONM and INM is continuous with the ER lumen (in light green). Most proteins (blue spheres) and ribosomes (not shown) that reside in the peripheral ER can diffuse to the ONM. However, some proteins, such as the reticulons (in yellow), are confined to highly curved membrane; they are enriched in the peripheral ER that is in the form of tubules, and are present in the curved memrbane that is around the NPCs (not shown). The protein composition of the INM (purple spheres) is distinct from that of the ONM. Underlying the INM is the nuclear lamina (brown meshwork). The LINC complex (in green) spans the ONM and INM (see Fig. 2). b: A cross section through the NPC, with its main parts highlighted. Note that each of the structures shown is made up of various proteins.

Fig. 2

The LINC complex. The LINC complex is composed of two protein types: a KASH-domain protein (light green), which spans the ONM, and a SUN-domain protein (dark green), which spans the INM. The KASH and SUN domain proteins interact in the NE lumen via their respective domains (striated regions). KASH-domain proteins interact in the cytoplasm with elements of the cytoskeleton (red), such as microtubules and actin cable. SUN-domain proteins interact in the nucleoplasm with the nuclear lamina (brown mesh-work).

Fig. 3

Uneven expansion of the budding yeast nucleus. In wild type budding yeast, the nucleolus (in red) forms a crescent shaped structure apposing the NE (in green) that caps the chromatin (in blue). In spo7Δ, nem1Δ, or pah1Δ mutant cells, the NE expands only in the region that is adjacent to the nucleolus, forming a “flare”, while the NE adjacent to the chromatin retains it original shape.

Fig. 4

Changes in nuclear shape in response to increase in NE surface area. In a hypothetical situation where the NE surface area (SA = x) of a nucleus with a given volume (volume = y) increases by 20%, the nucleus can change in shape in one of two ways: a: The NE can expand uniformly. In this case, a 20% increase in SA will result in a 30% increase in nuclear volume. b: The NE can form invaginations and/or protrusions such that nuclear volume remains unchanged. The dashed red line shows the circumference of the original nucleus, before NE expansion.