從受精到卵中胞質(zhì)Ca2+濃度增加(多細(xì)胞生物卵激發(fā)過(guò)程中的一個(gè)至關(guān)重要的事件)的通道已經(jīng)明確確定了,,但對(duì)其下游通道的研究卻不是很多,。 現(xiàn)在,,兩個(gè)研究小組報(bào)告了這方面的研究,。他們發(fā)現(xiàn)了一個(gè)新的涉及磷酸酶,、鈣調(diào)神經(jīng)磷酸酶的通道,。由鈣誘導(dǎo)的鈣調(diào)神經(jīng)磷酸酶的激發(fā),,對(duì)于Xeonopus中胚胎發(fā)育的抑制是必不可少的,,促使卵母細(xì)胞走出受精之后減數(shù)分裂的M-階段中的細(xì)胞周期抑制時(shí)期,。然后,第二波磷酸酶活動(dòng)則充當(dāng)進(jìn)入有絲分裂的一個(gè)通道,。
原始出處:
Nature 449, 336-340 (20 September 2007) | doi:10.1038/nature06121; Received 4 May 2007; Accepted 26 July 2007
Calcineurin is required to release Xenopus egg extracts from meiotic M phase
Satoru Mochida1 & Tim Hunt1
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Correspondence to: Tim Hunt1 Correspondence and requests for materials should be addressed to T.H. (Email: [email protected]).
Fertilization induces a transient increase in cytoplasmic Ca2+ concentration in animal eggs that releases them from cell cycle arrest in the second meiotic metaphase1. In frog eggs, Ca2+ activates Ca2+/calmodulin-activated kinase, which inactivates cytostatic factor2, 3, 4, 5, allowing the anaphase-promoting factor to turn on and ubiquitinate cyclins and securin, which returns the cell cycle to interphase6. Here we show that the calcium-activated protein phosphatase calcineurin7 is also important in this process. Calcineurin is transiently activated after adding Ca2+ to egg extracts, and inhibitors of calcineurin such as cyclosporin A (ref. 8) delay the destruction of cyclins, the global dephosphorylation of M-phase-specific phosphoproteins and the re-formation of a fully functional nuclear envelope. We found that a second wave of phosphatase activity directed at mitotic phosphoproteins appears after the spike of calcineurin activity. This activity disappeared the next time the extract entered M phase and reappeared at the end of mitosis. We surmise that inhibition of this second phosphatase activity is important in allowing cells to enter mitosis, and, conversely, that its activation is required for a timely return to interphase. Calcineurin is required to break the deep cell cycle arrest imposed by the Mos-MAP (mitogen-activated protein) kinase pathway4, 5, 9, and we show that Fizzy/Cdc20, a key regulator of the anaphase-promoting factor6, is an excellent substrate for this phosphatase.