TY  - GEN
AV  - public
Y1  - 2016///
TI  - The molecular mechanism of surface contraction waves in the starfish oocyte
ID  - heidok21578
A1  - Bischof, Johanna
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/21578/
N2  - The cortex is a contractile cross-linked network of actin filaments and myosin motors lining the plasma membrane. It defines the shape of animal cells, and regulated changes in cortex mechanics drive many cellular processes, including cell migration and division. The molecular mechanisms controlling cortical contractility in space and time are therefore essential for cell physiology, but are still not well understood. 
During cell division, in cytokinesis, tightly controlled changes to cortical contractility separate the two daughter cells. When very large cells undergo cell divisions, they exhibit highly stereotypical patterns of cortical contractility, termed surface contraction waves (SCWs). These waves occur in cells of a wide variety of species and move across the cells immediately prior to the division. The molecular mechanisms underlying this striking phenomenon are not known.
I set out to investigate SCWs in starfish oocytes, which display a prominent contraction wave during meiotic division that can be imaged live using fluorescence microscopy. Combined with quantitative image analysis, this allowed me to correlate cell shape changes with the localization of key cortical and cell cycle proteins in untreated oocytes and following biochemical and physical manipulations. 
I find that morphologically the contraction wave is a band of flattening that forms at the vegetal pole and moves across the cell to the animal pole. The flattening is driven by increased cortical contractility induced by localisation of myosin II to the cortex. Myosin II recruitment is controlled by RhoA kinase and RhoA, which in turn is activated by release of its inhibition by the cell cycle kinase, cdk1-cyclin B. Importantly, I could show that cdk1-cyclin B activity forms a gradient along the animal-vegetal axis originating from accumulation of cdk1-cyclin B in the nucleus which is located at the animal pole. Therefore, as cyclin B is degraded, the bottom threshold of cdk1 activity will be reached first opposite of the animal pole, marking the starting point of the contraction wave. The gradient of cdk1-cyclin B activity furthermore controls the progression of the contraction wave across the cell. Additionally, I show that feedback internal to the downstream signalling network contributes to defining the speed of the wave and determines the width of the band of activity.
Overall, this data for the first time establishes the molecular mechanisms underlying SCWs, a phenomenon observed in oocytes of many species. I show that the contraction wave is driven by the highly conserved RhoA-Rok-Myosin II pathway, and is patterned in space and time by an activity gradient of cdk1 as well as feedbacks internal to the signalling pathway. My work thereby reveals how this biochemical signalling network can define a spatially and temporally complex cellular behaviour.
ER  -