AIP1 acts with cofilin to control actin dynamics during epithelial morphogenesis

Abstract

SUMMARYDuring epithelial morphogenesis, cells not only maintain tight adhesion for epithelial integrity but also allow dynamic intercellular movement to take place within cell sheets. How these seemingly opposing processes are coordinated is not well understood. Here, we report that the actin disassembly factors AIP1 and cofilin are required for remodeling of adherens junctions (AJs) during ommatidial precluster formation in Drosophila eye epithelium, a highly stereotyped cell rearrangement process which we describe in detail in our live imaging study. AIP1 is enriched together with F-actin in the apical region of preclusters, whereas cofilin displays a diffuse and uniform localization pattern. Cofilin overexpression completely rescues AJ remodeling defects caused by AIP1 loss of function, and cofilin physically interacts with AIP1. Pharmacological reduction of actin turnover results in similar AJ remodeling defects and decreased turnover of E-cadherin, which also results from AIP1 deficiency, whereas an F-actin-destabilizing drug affects AJ maintenance and epithelial integrity. Together with other data on actin polymerization, our results suggest that AIP1 enhances cofilin-mediated actin disassembly in the apical region of precluster cells to promote remodeling of AJs and thus intercellular movement, but also that robust actin polymerization promotes AJ general adhesion and integrity during the remodeling process.

Jack of all trades: functional modularity in the adherens junction

“…For instance, in epithelial cells neural Wiskott-Aldrich Syndrome Protein (N-WASP) works with WIRE to stabilize F-actin, though the mechanism is not yet understood [45]. Conversely, the actin severing proteins AIP1 and cofilin are needed for destabilization and remodeling of AJ [46].…”

Guidance receptor promotes the asymmetric distribution of exocyst and recycling endosome during collective cell migration

“…Ovaries were dissected and cultured in Schneider's medium cocktail as described previously for use of live imaging (Chu et al, 2012;Prasad and Montell, 2007). After dissection, egg chambers were incubated in Latrunculin A (2 μM in Schneider's medium cocktail, Invitrogen) for 1 hour before fixation, and were then stained as described above.…”

GMF Promotes Leading-Edge Dynamics and Collective Cell Migration In Vivo

“…This protein promotes rapid actin turnover by interacting with cofilin-decorated actin filaments and enhancing their disassembly [31–34]. In Drosophila , inactivation of the Aip1 homolog Flare causes defects similar to cofilin ( Twinstar ) mutants, including accumulation of excess F-actin and increased stability of actin networks [35, 36]. Our experiments revealed that Aip1 silencing caused F-actin accumulation and moderate border cell migration delays as detected from fixed stage 10 egg chambers.…”