Role of non-junctional cadherins in regulating the cortex

Several years ago we made the surprising discovery that E-cadherin formed clusters all over the cell membrane, independently of cell-cell junctions. We went on to show that these clusters, which are delimited by cortical F-actin, can become adhesive clusters when they come in contact with another cell and form cell-cell junctions when they congregate at high density. This work was published in Dev Cell 32(2):139-54. However, we were left with an open question: do non-adhesive cadherins have a role outside of cell-cell junctions, aside from being building material for junctions?

Screen Shot 2017-05-09 at 10.23.32 PM

An answer to that question came from experiments we performed in C. elegans. We discovered the nematode ortholog of E-cadherin, HMR-1, also forms non-junctional clusters in the early embryo and they affect cortical dynamics.

Screen Shot 2017-05-09 at 10.26.05 PM

Non-junctional cadherin clusters were found to inhibit Rho-1 and the level of non-muscle myosin II at the cortex. Moreover, non-junctional cadherin increased the friction between cortical actomyosin and the membrane and slowed cortical flows. This resulted in C. elegans cadherin slowing down cytokinesis as can be seen in the following figure:

Screen Shot 2017-05-09 at 10.27.30 PM
Perhaps the most remarkable phenotype we observed with the depletion of HMR-1/E-cadherin in the C. elegans zygotes occured in about 10% of the zygotes: a complete detachment of the actomyosin cortex from the plasma membrane:

This phenotype raises many questions about the regulation of cortical dynamics in the absence of membrane. We are now optimising conditions in which this phenotype will be highly penetrant and robust so we can address those questions.

In parallel, we are also currently investigating the role of mammalian cadherins in regulating cortical dynamics outside of cell-cell junctions. Preliminary results in single mammary epithelial cells indicate that such a role is conserved.