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bioRxiv · 10.1101/2023.03.17.533017

Pten, Pi3K and PtdIns(3,4,5)P3 dynamics modulate pulsatile actin branching in Drosophila retina morphogenesis

Malin, J.·Rosa Birriel, C.·Hatini, V.
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Abstract

Epithelial remodeling of the Drosophila retina depends on the pulsatile contraction and expansion of apical contacts between the cells that form its hexagonal lattice. Phosphoinositide PI(3,4,5)P3 (PIP3) accumulates around tricellular adherens junctions (tAJs) during contact expansion and dissipates during contraction, but with unknown function. Here we found that manipulations of Pten or Pi3K that either decreased or increased PIP3 resulted in shortened contacts and a disordered lattice, indicating a requirement for PIP3 dynamics and turnover. These phenotypes are caused by a loss of protrusive branched actin, resulting from impaired activity of the Rac1 Rho GTPase and the WAVE regulatory complex (WRC). We additionally found that during contact expansion, Pi3K moves into tAJs to promote the cyclical increase of PIP3 in a spatially and temporally precise manner. Thus, dynamic regulation of PIP3 by Pten and Pi3K controls the protrusive phase of junctional remodeling, which is essential for planar epithelial morphogenesis. Graphical Abstract: Control of contact length by Pi3K, Pten and PIP3. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/533017v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@bef175org.highwire.dtl.DTLVardef@1de40e9org.highwire.dtl.DTLVardef@77b645org.highwire.dtl.DTLVardef@15f84df_HPS_FORMAT_FIGEXP M_FIG C_FIG Pi3K regulates the transition from contraction to expansion through its tension-dependent localization to tAJs and modulation of its lipid phosphatase activity. Pten localizes uniformly to regulate PIP3 turnover and attenuate PIP3 production. (A) Tension shortens contacts, concentrates Pi3K at four spots at a distance from tAJs, and inhibits Pi3Ks lipid phosphatase function. (B) High tension ultimately disassembles contractile networks allowing Pi3K to flow toward tAJs, produce PIP3 and activate the WRC to promote actin branching and contact expansion. (C) High protrusion in expanded contacts disperses the WRC and disassembles the branched actin network. (D) Branched actin disassembly allows the assembly and contraction of an actomyosin network, which increases tension and contracts the contact leading to the flow of Pi3K away from tAJs and inhibition of its lipid phosphatase function, thus completing the cycle.

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Malin, J., Rosa Birriel, C., Hatini, V.. 2023-03-18. Pten, Pi3K and PtdIns(3,4,5)P3 dynamics modulate pulsatile actin branching in Drosophila retina morphogenesis. https://doi.org/10.1101/2023.03.17.533017

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