Intercalate or invaginate: PI(3,4,5)P3 governs a membrane constriction switch in cell shaping

Autor: Gonzalo Herranz, Fernando Martín-Belmonte, Gabriel Baonza
Rok vydání: 2021
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Zdroj: Dev Cell
Digital.CSIC. Repositorio Institucional del CSIC
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Popis: Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating contractile forces before cyclically disassembling. This pulsed nature of cytoskeletal forces implies 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)P(3) is a critical lipid-based cue for ratcheting engagement. The Sbf RabGEF binds to PIP(3), and disruption of PIP(3) reveals a dramatic switching behavior in which medial ratcheting is activated and epithelial cells begin globally constricting apical surfaces. PIP(3) enrichments are developmentally regulated, with mesodermal cells having high apical PIP(3) while germband cells have higher interfacial PIP(3). 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.
Databáze: OpenAIRE