New insights into proteolytic activity.

© 2011 EPFL

© 2011 EPFL

The microenvironment patterns the pluripotent mouse epiblast through paracrine Furin and Pace4 proteolytic activities.

According to text books, proprotein convertases activate a host of important regulatory proteins during their passage through secretory vesicles. However, this view could not explain recent genetic data from the group of Prof. Daniel Constam (UPCDA - Constam Lab) that at least two members of this protease family somehow activated a master regulator of cell fate in the mouse blastocyst "remotely" in pluripotent progenitors that do not themselves produce any of these enzymes. Resolving this conundrum, a recent study shows that secreted forms of these proteolytic activities provided by cells in the microenvironment move across several cell diameters through the extracellular space, and that they are active in recipient cells and sufficient to specify their subsequent allocation to different germ layers.

Daniel Mesnard et al., Genes & Dev. 25: 1871-1880, doi: 10.1101/gad.16738711 (2011)