Polyamines and cell migration

Leeuwenhoek first described polyamines in 1677, but active investigation di d not begin until the 1970's. When intracellular polyamine levels are reduc ed by inhibitors, mutation, or transfection, severe reductions occur in cel l division, cell differentiation, and cell migration. These effects are not difficult to demonstrate and measure, and all can be prevented if suppleme ntal exogenous polyamines are supplied. However, linking the overall effect s to molecular events remains to be accomplished. In this review, we discus s work (mostly from the last 10 years) that relates to cell migration. Spec ifically, 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 significantl y. These are: 1) the regulation of intracellular Ca++ concentration by volt age-gated K+ channels, 2) the maintenance of normal RhoA levels that, with Rac, regulate the assembly of actin stress fibers, focal adhesions, and con tractility, 3) the formation of ATP-Mg++-polyamine trimers that enhance the phosphorylation activity of ATP toward enzymes in specific signaling pathw ays and, 4) alterations in the structure of RNA that change translation ini tiation sites and affect the expression of proteins.