Drosophila PI4KIIIalpha is required in follicle cells for oocyte polarization and Hippo signaling

Abstract

SUMMARYIn a genetic screen we isolated mutations in CG10260, which encodes a phosphatidylinositol 4-kinase (PI4KIIIalpha), and found that PI4KIIIalpha is required for Hippo signaling in Drosophila ovarian follicle cells. PI4KIIIalpha mutations in the posterior follicle cells lead to oocyte polarization defects similar to those caused by mutations in the Hippo signaling pathway. PI4KIIIalpha mutations also cause misexpression of well-established Hippo signaling targets. The Merlin-Expanded-Kibra complex is required at the apical membrane for Hippo activity. In PI4KIIIalpha mutant follicle cells, Merlin fails to localize to the apical domain. Our analysis of PI4KIIIalpha mutants provides a new link in Hippo signal transduction from the cell membrane to its core kinase cascade.

PI4KIIIα is required for cortical integrity and cell polarity during Drosophila oogenesis

“…Indeed, based on previously reported links between Oskar and F-actin (Krauss et al, 2009;Tanaka et al, 2011), PI4KIIIa may stimulate a positive feedback loop that coordinates phosphoinositides, actin organization, membrane trafficking and cell polarization. PI4KIIIa was previously shown to be required in posterior follicle cells (PFCs) to control Hippo signaling, which in turn regulates oocyte nucleus migration and localization of the posterior polarity determinant Staufen (Yan et al, 2011). These defects are similar to those seen in PI4KIIIa GLCs.…”

“…However, our observations suggest that PI4KIIIa probably regulates distinct molecular events in PFCs and the oocyte to control oocyte nucleus migration. In egg chambers with PI4KIIIa mutant PFCs, the oocyte nucleus is consistently positioned tightly at the posterior, indicating that mutant PFCs fail to send the unknown signal that initiates oocyte repolarization (Yan et al, 2011). In contrast, the oocyte nucleus in PI4KIIIa GLCs is found in the middle of the oocyte, suggesting that a PI4KIIIa mutant germline is capable of receiving the unknown signal initiating nucleus migration, but fails to complete the process.…”

“…Indeed, genetic interactions indicate that Hedgehog relieves Patched inhibition of Drosophila PI4KIIIa, suggesting that PI4KIIIa activity is regulated (Yavari et al, 2010). PI4KIIIa also promotes FGF signaling in zebrafish (Ma et al, 2009), Hippo signaling in flies (Yan et al, 2011) and MAPK signaling in yeast (Garrenton et al, 2010). Hence, a crucial and conserved property of this enzyme is to control lipids at the PM, thereby relaying signals to molecular effectors at the cell cortex.…”

“…PI4Ks are crucial for cell homeostasis, yet only a handful of studies address their functions in multicellular organisms (Brill et al, 2000;Burgess et al, 2012;Khuong et al, 2010;Ma et al, 2009;Polevoy et al, 2009;Raghu et al, 2009;Simons et al, 2009;Yan et al, 2011;Yavari et al, 2010). A recent report examining mouse PI4KIIIa revealed transient localization of PI4KIIIa to the PM (Nakatsu et al, 2012).…”

Multiple Roles for Egalitarian in Polarization of the Drosophila Egg Chamber

“…Once posterior fate has been specified, the follicle cells signal back to the oocyte. Although the nature of this signal is still unknown, the Notch and Hippo pathways are thought to contribute to the process (Ruohola et al 1991;Meignin et al 2007;Polesello and Tapon 2007;Yu et al 2008;Yan et al 2011). In addition, proteins within the extracellular matrix and factors that link the oocyte to the follicle cells are also involved (Deng and Ruohola-Baker 2000;Frydman and Spradling 2001;MacDougall et al 2001).…”