A PtdIns(3,4,5)P 3 dispersal switch engages cell ratcheting at specific cell surfaces

Dev Cell. 2021 Sep 27;56(18):2579-2591.e4. doi: 10.1016/j.devcel.2021.08.016. Epub 2021 Sep 14.


Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating contractile forces before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be ratcheting mechanisms that drive processive transformations in cell shape. Previous work has shown that force generation is coordinated with endocytic remodeling; however, how ratcheting becomes engaged at specific cell surfaces remains unclear. Here, we report that PtdIns(3,4,5)P3 is a critical lipid-based cue for ratcheting engagement. The Sbf RabGEF binds to PIP3, and disruption of PIP3 reveals a dramatic switching behavior in which medial ratcheting is activated and epithelial cells begin globally constricting apical surfaces. PIP3 enrichments are developmentally regulated, with mesodermal cells having high apical PIP3 while germband cells have higher interfacial PIP3. Finally, we show that JAK/STAT signaling constitutes a second pathway that combinatorially regulates Sbf/Rab35 recruitment. Our results elucidate a complex lipid-dependent regulatory machinery that directs ratcheting engagement in epithelial tissues.

Keywords: Drosophila; apical constriction; cell intercalation; cell ratcheting; gastrulation; membrane trafficking; morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural