Figure 12–16 Feedback regulation of cholesterol biosynthesis. sreBp (sterol response element binding protein), a latent transcription regulator that controls expression of cholesterol biosynthetic enzymes, is initially synthesized as an er membrane protein. it is anchored in the er if there is sufficient cholesterol in the membrane by interaction with another er membrane protein, called sCap (sreBp cleavage activation protein), which binds cholesterol. if the cholesterol binding site on sCap is empty (at low cholesterol concentrations), sCap changes conformation and is packaged together with sreBp into transport vesicles, which deliver their cargo to the Golgi apparatus, where two Golgi-resident proteases cleave sreBp to free its cytosolic domain from the membrane. The cytosolic domain then moves into the nucleus, where it binds to the promoters of genes that encode proteins involved in cholesterol biosynthesis and activates their transcription. in this way, more cholesterol is made when its concentration falls below a threshold.
Figure 12–17 The nuclear lamina. an electron micrograph of a portion of the nuclear lamina in a Xenopus oocyte prepared by freeze-drying and metal shadowing. The lamina is formed by a regular lattice of specialized intermediate filaments. lamins are only present in metazoan cells. other, yet-unknown proteins may serve similar functions in species that lack lamins. (Courtesy of Ueli aebi.) complex inner nuclear membrane outer nuclear membranenuclear envelope PHOSPHORYLATION OF LAMINS AND NPC PROTEINS DEPHOSPHORYLATION OF LAMINS FUSION OF ENVELOPED CHROMOSOMES FUSION OF NUCLEAR ENVELOPE FRAGMENTS nuclear envelope fragmentduplicated chromosome daughter chromosome phosphorylated lamins INTERPHASE NUCLEUS EARLY TELOPHASE PROPHASE LATE TELOPHASE nuclear pore complex proteins P P P P P P P P P P P P P P P P Figure 12–18 The breakdown and re-formation of the nuclear envelope and lamina during mitosis. phosphorylation of the lamins triggers the disassembly to the chromosome surface, where they assemble into new NPCs. At the same time, inner nuclear membrane proteins and dephosphorylated lamins bind again to chromatin. ER membranes wrap around groups of chromosomes until they form a sealed nuclear envelope (Movie 12.2). During this process, the NPCs start actively re-importing proteins that contain nuclear localization signals. Because the nuclear envelope is initially closely applied to the surface of the chromosomes, the newly formed nucleus excludes all proteins except those initially bound to the mitotic chromosomes and those that are selectively imported through NPCs. In this way, all other large proteins, including ribosomes, are kept out of the newly assembled nucleus.
As we discuss in Chapter 17, the cloud of Ran-GTP surrounding chromatin is also important in assembling the mitotic spindle in a dividing cell.
The nuclear envelope consists of an inner and an outer nuclear membrane that are continuous with each other and with the ER membrane, and the space between the inner and outer nuclear membrane is continuous with the ER lumen. RNA molecules, which are made in the nucleus, and ribosomal subunits, which are assembled there, are exported to the cytosol; in contrast, all the proteins that function in the nucleus are synthesized in the cytosol and are then imported. The extensive traffic of materials between the nucleus and cytosol occurs through nuclear pore complexes (NPCs), which provide a direct passageway across the nuclear envelope. Small molecules diffuse passively through the NPCs, but large macromolecules have to be actively transported.