It's a midwest nice thing: "Cells divide; We don't have to"

For the fans of other #junctions, we extract and RE-PRESENT previously buried Supplemental Data (lots of changes in TJ and Desmosome junction proteins). 9/10

But there IS A CATCH—phospho-specific antibodies to alpha-cat DON’T JUST label mitotic cells, but ALL adherens junctions. 7/10

While we knew phospho-sites were REQUIRED for adhesive strength, upstream PROCESSES that promote alpha-cat phosphorylation remained 🤔 3/10

Relevance to #disease? Missense mutations in alpha-cat are associated with #ButterflyPatternDystrophy- an age-dependent #eye disease that initiates via progressive binucleation and multinucleation of RPE. 10/12 www.nature.com/articles/ng....

Since epithelial #cytokinesis/abscission resolves at the level of #apicaljunctions, conditions where alpha-cat becomes persistently unfolded may interfere—and this could drive binucleation in cells that use this #polyploid state. 9/12

We then show reductions in LZTS2 led to binucleation, and an alpha-cat mutant with a persistently OPEN “middle region” super-sequesters LZTS2, depleting it from where needed for abscission. 8/12

Curiously, LZTS2 localizes to #basal bodies #centrosomes #midbody BUT ALSO #apicaljunctions. LZTS2 was also enriched in two recent BioID screens with the AJ/TJ component Afadin (Manser and @peiferlabunc.bsky.social labs). So LZTS2 seemed like a good target. 7/12

We leveraged a #BioID screen conceived by @pmresearch-uhn.bsky.social Noboru Ishiyama/Mitsu Ikura and @gingraslab.bsky.social —finding candidates that bind OPEN vs closed alpha-cat. A reasonable candidate was LZTS2—previously implicated in #abscission, but poorly understood. 6/12

Adhering to the view that one can understand normal biology through rationally-designed mutants— we discovered that an alpha-catenin with altered force-dependent binding to actin leads to cytokinesis failures. 2/12