Cell Size Control: New Evidence for a General Mechanism

Continuously proliferating cells have to precisely double their size during each cycle to maintain constant volumes. Time and again, this fact raised questions on the existence of an active cell size control mechanism in eukaryotic cells, which would prevent delayed or premature cell division at inadequate mass. We addressed this open issue by recapitulating in animal cells several long-standing experiments which had identified such a mechanism in yeast. As a model, mainly chicken erythroblasts were used, whose proliferation can be driven either by a constitutively active oncogene (v-ErbB) or the physiological cytokines stem cell factor + erythropoietin. V-ErbB-driven cells proliferated faster than Epo/SCF-driven cells (doubling time 13 vs. 22 hours) and exhibited a 1.4-fold increased cell volume, due to a two-fold higher rate of global protein synthesis. Rapid and complete phenotypic reversion was achieved by exchanging the respective factors. To analyze the switch from one proliferation mode to the other in detail, we followed cell cycle progression of cells re-cultivated after synchronization by centrifugal elutriation. The results indicated that altered protein synthesis rates exclusively influenced G1 phase duration. Additional experiments with chicken erythroblasts and mammalian fibroblasts treated with low doses of aphidicolin (artificially prolonging S-phase) also pointed to the existence of a general size sensing mechanism in G1, ensuring cell size maintenance over many divisions, probably similar to the situation in yeast but certainly regulated at additional levels in higher eukaryotes.