Signal Transduction to the Cell Nucleus

This chapter has emphasized dynamic aspects of intracellular organization. Signal transduction from cytoplasm to nucleus was proposed to depend on the existence of equilibria in protein distributions across the nuclear envelope, and on various mechanisms controlling the subcellular distribution of regulatory macromolecules. Prominent roles in the control of nucleocytoplasmic protein distributions were attributed to cytoplasmic anchorage-release or NLS-masking/unmasking mechanisms, and to posttranslational modifications, notably phosphorylation. Although the notions presented here may contribute to the rationalization of experimental findings in several different systems, it should be emphasized that other fundamentally different mechanisms of signal transduction to the nucleus are not excluded. For instance, it is obvious that nuclear activities depend on the availability of cytoplasmically produced metabolites (e.g., building blocks required for nucleic acid synthesis). The regulation of the cytoplasmic production of such components clearly provides a means to modulate nuclear activities. Also, it is possible to entertain models of signal transduction based on purely mechanical aspects of cellular organization. For instance, there is no doubt that the extracellular matrix is linked across the plasma membrane to the cytoskeleton (e.g., Burridge, 1986), and interactions between the cytoskeleton and karyoskeletal proteins have also been proposed (Fey et al., 1984; Georgatos and Blobel, 1987a,b; Fey and Penman, 1988). Alterations in cell morphology are well known to influence patterns of gene expression (e.g., Benecke et al., 1978; Farmer et al., 1983), and it is an interesting question, therefore, to what extent changes in nuclear activities can be attributed directly to changes in the architecture of the cytoskeleton and the nucleoskeleton