Figure 16–71 Plectin cross-linking of diverse cytoskeletal elements. Plectin (green) is seen here making cross-links from intermediate filaments (blue) to microtubules (red). In this electron micrograph, the dots (yellow) are gold particles linked to anti-plectin antibodies. The entire actin filament network was removed to reveal these proteins. (From
T.M. Svitkina et al., J. Cell Biol. 135:991– 1007, 1996. With permission from The Rockefeller University Press.) of the inner nuclear membrane and KASH proteins (also called nesprins) of the outer nuclear membrane (Figure 16–72). SUN and KASH proteins bind to each other within the lumen of the nuclear envelope, forming a bridge that connects the nuclear and cytoplasmic cytoskeletons. Inside the nucleus, the SUN proteins bind to the nuclear lamina or chromosomes, whereas in the cytoplasm, KASH proteins can bind directly to actin filaments and indirectly to microtubules and intermediate filaments through association with motor proteins and plakins, respectively. This linkage serves to mechanically couple the nucleus to the cytoskeleton and is involved in many cellular functions, including chromosome movements inside the nucleus during meiosis, nuclear and centrosome positioning, nuclear migration, and global cytoskeletal organization.
Mutations in the gene for plectin cause a devastating human disease that combines epidermolysis bullosa (caused by disruption of skin keratin filaments), muscular dystrophy (caused by disruption of desmin filaments), and neurodegeneration (caused by disruption of neurofilaments). Mice lacking a functional plectin gene die within a few days of birth, with blistered skin and abnormal skeletal and heart muscles. Thus, although plectin may not be necessary for the initial formation and assembly of intermediate filaments, its cross-linking action is required to provide cells with the strength they need to withstand the mechanical stresses inherent to vertebrate life.
GTP-binding proteins called septins serve as an additional filament system in all eukaryotes except terrestrial plants. Septins assemble into nonpolar filaments that form rings and cagelike structures, which act as scaffolds to compartmentalize membranes into distinct domains, or recruit and organize the actin and microtubule cytoskeletons. First identified in budding yeast, septin filaments localize to the neck between a dividing yeast mother cell and its growing bud (Figure 16–73A). At this location, septins block the movement of proteins from one side of the bud neck to the other, thereby concentrating cell growth preferentially within the bud. Septins also recruit the actin–myosin machinery that forms the contractile ring required for cytokinesis. In animal cells, septins function in cell division, migration, and vesicle trafficking. In primary cilia, for example, a ring of septin filaments assembles at the base of the cilium and serves as a diffusion barrier at the plasma membrane, restricting the movement of membrane proteins and establishing a specific composition in the ciliary membrane (Figure 16–73B and C). Reduction of septin levels impairs primary cilium formation and signaling.
There are 7 septin genes in yeast and 13 in human, and septin proteins fall into four groups on the basis of sequence relationships. In a test tube, purified septins assemble into symmetrical hetero-hexamers or hetero–octamers that