Second meiotic arrest and exit in frogs and mice

Abstract

Mature vertebrate oocytes typically undergo programmed arrest at the second meiotic cell cycle until they are signalled to initiate embryonic development at fertilization. Here, we describe the underlying molecular mechanisms of this second meiotic arrest and release in Xenopus, and compare and contrast them with their counterparts in mice.

Figure 1

Composite schematic of endogenous meiotic inhibitor 2 regulation in vertebrates. Details of selected interactions are described in the text. APC, anaphase promoting complex; Calm, calmodulin; Camk2, calmodulin-dependent kinase 2; Can, calcineurin; Cdc2/20, cell division cycle 2/20 homologues, respectively; Cdc2:Cycb, maturation promoting factor; Cycb, cyclin B; Emi2, endogenous meiotic inhibitor 2; IP₃, inositol 1,4,5-trisphosphate; IP₃R_c, closed IP₃ receptor; IP₃R_o, open IP₃ receptor; Mapk, mitogen-activated protein kinase; Mek, mitogen-activated protein kinase kinase; PIP₂, phosphatidylinositol 4,5-bisphosphate; Plcz1, phospholipase C-zeta; Plk1, polo-like kinase 1; PP2A, protein phosphatase 2A; Rsk, ribosomal s6 kinase; SCF, Skp1– Cullin– F-box-containing E3 ubiquitin ligase complex; Trcp1b, F-box protein β-transducin repeat containing protein 1b; Ub, ubiquitin; P, phosphate; *, active form; Δ[Ca²⁺]_i, increase in the intracellular free calcium ion concentration.

Figure 2

Pairwise alignment of mouse (Mus, top) and frog (Xenopus, bottom) endogenous meiotic inhibitor 2 predicted amino-acid sequences, showing identities as red bars beneath. The alignment was based on one produced by BLAST. Key portions of the alignment (described in the text) are expanded, showing residues identical to the mouse sequence in black, non-identical ones in grey and those subject to phosphorylation in red, with their corresponding kinases and/or phosphatases. Information directing mII establishment and/or maintenance apparently resides in the carboxy-terminal 70%, with the amino-terminal 30% containing elements that direct mII exit. The F-box and the zinc-binding region (ZBR) are as delineated by Schmidt et al (2005). Abbreviations are as for Fig 1.

Figure 3

Low-resolution model of second metaphase homeostasis. The model links spindle modulation by Mos to the establishment and maintenance of, and exit from, Emi2-mediated mII arrest. The establishment of Emi2 as cytostatic factor (Emi2^CSF) is coordinated by mII spindle formation (spindle^*) and Mos activity. Following fertilization, Emi2^CSF is replaced by Emi2^cyk activity which modulates Mos function (Mos^*) to ensure that the spindle is formatted for productive cytokinesis (spindle⁺).

Anthony C.F. Perry

Marie-Hélène Verlhac