Polyamines and cell migration.

Leeuwenhoek first described polyamines in 1677, but active investigation did not begin until the 1970's. When intracellular polyamine levels are reduced by inhibitors, mutation, or transfection, severe reductions occur in cell division, cell differentiation, and cell migration. These effects are not difficult to demonstrate and measure, and all can be prevented if supplemental exogenous polyamines are supplied. However, linking the overall effects to molecular events remains to be accomplished. In this review, we discuss work (mostly from the last 10 years) that relates to cell migration. Specifically, we have discussed the biology and biochemistry of the polyamines, their transport and regulation, the structure of the cytoskeleton and the mechanics of cell movement. We have also considered four specific processes that polyamines participate in that may affect cell migration significantly. These are: 1) the regulation of intracellular Ca++ concentration by voltage-gated K+ channels, 2) the maintenance of normal RhoA levels that, with Rac, regulate the assembly of actin stress fibers, focal adhesions, and contractility, 3) the formation of ATP-Mg++-polyamine trimers that enhance the phosphorylation activity of ATP toward enzymes in specific signaling pathways and, 4) alterations in the structure of RNA that change translation initiation sites and affect the expression of proteins.