Maturing from Memory

Abstract

Xenopus oocytes arrest during meiosis and complete the maturation process in response to stimulation by progesterone. Maturation involves the activation of two kinases, p42 mitogen-activated protein kinase (p42 MAPK) and the cell division cycle protein kinase Cdc2, which are involved in positive-feedback loops that stimulate their own and each other's activity. Xiong and Ferrell determined that although progesterone was required to initiate maturation, germinal vesicle breakdown (GVBD) and the activity of the two kinases (p42 MAPK and Cdc2) persisted after progesterone had been washed away from the oocytes. Using a Raf-estrogen receptor chimera to directly stimulate p42 MAPK with estrogen (instead of through the cell surface progesterone receptor), the authors showed that, as with progesterone, once the oocytes were committed to maturation by the initial exposure to estrogen that estrogen was not required to maintain GVBD and Cdc2 and p42 MAPK activity. If positive feedback was blocked by inhibition of protein synthesis, or inhibition of either of the two kinases upstream of p42 MAPK, Mos or MEK, then p42 MAPK and Cdc2 activities were transiently and not irreversibly stimulated by the initial exposure to estrogen. These results show that positive feedback, which has long been proposed to transform signals from transient to self-sustaining, serves as a memory of past stimulation to convert a transient initial stimulus into an irreversible system-level change in activity. W. Xiong, J. E. Ferrell Jr., A positive-feedback-based bistable "memory module" that governs a cell fate decision. Nature 426 , 460-465 (2003). [Online Journal]