We show that in both epithelial and heart cells, desmoplakin behaves like a 'directional' force sensor, and responds to changes in tensile forces by undergoing a dramatic conformational change.

Desmosomes are adhesive junctions that mediate the integrity of tension prone tissues like the heart and the skin. Yet, how desmosomes sense and respond to mechanical stimuli are unknown. We show that actomyosin forces alter the conformation of desmoplakin, a key desmosomal protein.

We show that antibodies can trap cadherin in a distinct conformation (the X-dimer). Formation of stable X-dimers trigger the phosphorylation of p120-catenin, a suppressor of cadherin endocytosis. Consequently p120 dissociates from the X-dimer cytoplasmic region which causes cadherin endocytosis.

We demonstrate that an extracellular conformation of cadherin, an essential cell-cell adhesion protein, triggers cadherin internalization. Our work provides fundamental insights into how cells regulate adhesion and can be exploited to design antibodies for intracellular drug delivery.

Our study offers guidelines for designing antibodies that strengthen cadherin adhesion. We show that these antibodies stabilize the primary E-cadherin binding conformation and inhibit conformational changes during dissociation.

UC Davis has a nice blog post describing this research

We benchmark LAB against the widely used TurboID proximity labeling method by measuring the proteome of E-cadherin, an essential cell–cell adhesion protein. LAB can map E-cadherin-binding partners with higher accuracy and significantly fewer false positives than TurboID.

Our technology, called light-activated BioID (LAB), fuses the two halves of the split-TurboID proximity labeling enzyme to the photodimeric proteins CRY2 and CIB1. Upon illumination with blue light, CRY2 and CIB1 dimerize, reconstitute split-TurboID and initiate biotinylation.

Journal of Cell Science also routinely screens all images upon acceptance for publication for issues like high contrast images, uniform pixel intensity, etc....

My SRO informed me that if the government shuts down, the study section will still meet UNLESS government is still shutdown during the scheduled review panel time.