Impairment in nuclear lamina architecture or function is associated with certain genetic diseases (laminopathies) and apoptosis. Mutations in lamin A/C cause tissue-specifc diseases that affect striated muscle, adipose tissue, peripheral nerve or skeletal development, and premature aging. Recently, two hereditary forms of Emery-Dreifuss muscular dystrophy (EDMD) have been associated with mutations in either lamins or lamin receptors. The X-linked recessive form of EDMD is caused by mutations of emerin, while the autosomal dominant form of EDMD is caused by mutations in lamin A/C. In general, EDMD is characterized by an early-onset contractures of major tendons, very slow progressive muscle weakness, muscle wasting in the upper and lower limbs, and cardiomyopathy (weakening of the heart muscle).
The nuclear envelope has an array of openings called nuclear pores.
At numerous sites, the paired membranes of the nuclear envelope are punctuated by 70to 80-nm “openings” through the envelope. These nuclear pores are formed from the merging of the inner and outer membranes of the nuclear envelope. With an ordinary TEM, a diaphragmlike structure appears to cross the pore opening (Fig. 3.7). Often a small dense body is observed in the center of the opening (Fig. 3.8). Since such profiles are thought to represent either ribosomes or other protein complexes (transporters) captured during their passage through the pore at the time of fixation, the term central plug/transporter is commonly used to describe this feature.
With special techniques—such as negative staining and high-voltage transmission electron microscopy, or recently,
FIGURE 3.6 • Structure of the nuclear lamina. a. This schematic drawing shows the structure of the nuclear lamina adjacent to the inner nuclear membrane. The cut window in the nuclear lamina shows the DNA within the nucleus. Note that the nuclear envelope is pierced by nuclear pore complexes, which allow for selective bidirectional transport of molecules between nucleus and cytoplasm. b. Electron micrograph of a portion of the nuclear lamina from a Xenopus oocyte. It is formed by intermediate filaments (lamins) that are arranged in a square lattice. 43,000. (Adapted from Aebi U, Cohn J, Buhle L, Gerace L. The nuclear lamina is a meshwork of intermediate-type filaments. Nature 1986;323:560–564.) nuclear lamina DNAnucleus reticulum perinuclear space nuclear pore complex a bb cryoelectron tomography—the nuclear pore exhibits additional structural detail (see Fig. 3.8). Eight multidomain protein subunits arranged in an octagonal central framework at the periphery of each pore form a cylinderlike structure known as the nuclear pore complex (NPC). The NPC, which has an estimated total mass of 125  106 daltons, is composed of about 50 different nuclear pore complex proteins collectively referred to as nucleoporins (Nup proteins). This central framework is inserted between the cytoplasmic ring and the nuclear ring (Fig. 3.9). From the cytoplasmic ring, eight short protein fbrils protrude into the cytoplasm and point toward the center of the structure. The nucleoplasmic ring complex anchors a nuclear basket (or nuclear “cage” that resembles a fish trap) assembled from eight thin 50-nm-long filaments joined distally by an adjustable terminal ring 30 to 50 nm in diameter (see Fig. 3.9). The cylinder-shaped central framework encircles the central pore of the NPC, which acts as a close-fitting diaphragm or gated channel. In addition, each NPC contains one or more water-filled channels for transport of small molecules.
The NPC mediates bidirectional nucleocytoplasmic transport.