CELL CYCLE-DEPENDENT REGULATION OF CELLULAR ATP CONCENTRATION, AND DEPOLYMERIZATION OF THE INTERPHASE MICROTUBULAR NETWORK INDUCED BY ELEVATED CELLULAR ATP CONCENTRATION IN WHOLE FIBROBLASTS

In the present work, evidence is presented indicating that an increase d cellular ATP concentration during mitosis may, in conjunction with o ther factors [Verde et al., 1990: Nature 343:233-238; Andersen et al., 1994: J Cell Biol. 127:1289-1299], induce depolymerization of the int erphase microtubular network in cultured fibroblasts. It is shown here that the cellular ATP concentration varies through the cell cycle, re aching a peak at G(2)M- and minimum at late G(1)/early S-phase. Furthe rmore, we have found, using indirect immunofluorescent staining with a n antitubulin antibody, that depolymerization of the interphase microt ubular network may be induced by increasing the intracellular ATP conc entration in cultured fibroblasts from 2.2 mM to 4.1 mM. This may be o btained through addition of adenosine and P-i to the growth medium. Ou r results indicate that this effect of adenosine and P-i is not mediat ed via adenosine receptors, but through an elevated cellular ATP conce ntration. ATP is suggested to act through a concentration-dependent ef fect on the exchangeable GTP site on tubulin, and nor through the acti on of protein kinases or microtubule-associated proteins. (C) 1996 Wil ey-Liss, Inc.