No transcription, no problem: Protein phosphorylation changes and the transition from oocyte to embryo

Although mature oocytes are arrested in a differentiated state, they are provisioned with maternally-derived macromolecules that will start embryogenesis. The transition to embryogenesis, called 'egg activation', occurs without new transcription, even though it includes major cell changes like completing stalled meiosis, translating stored mRNAs, cytoskeletal remodeling, and changes to nuclear architecture. In most animals, egg activation is triggered by a rise in free calcium in the egg's cytoplasm, but we are only now beginning to understand how this induces the egg to transition to totipotency and proliferation. Here, we discuss the model that calcium-dependent protein kinases and phosphatases modify the phosphorylation landscape of the maternal proteome to activate the egg. We review recent phosphoproteomic mass spectrometry analyses that revealed broad phospho-regulation during egg activation, both in number of phospho-events and classes of regulated proteins. Our interspecies comparisons of these proteins pinpoints orthologs and protein families that are phospho-regulated in activating eggs, many of which function in hallmark events of egg activation, and others whose regulation and activity warrant further study. Finally, we discuss key phospho-regulating enzymes that may act apically or as intermediates in the phosphorylation cascades during egg activation. Knowing the regulators, targets, and effects of phospho-regulation that cause an egg to initiate embryogenesis is crucial at both fundamental and applied levels for understanding female fertility, embryo development, and cell-state transitions.