Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis

Abstract

E-cadherin plays a pivotal role in epithelial morphogenesis. It controls the intercellular adhesion required for tissue cohesion and anchors the actomyosin-driven tension needed to change cell shape. In the early Drosophila embryo, Myosin-II (Myo-II) controls the planar polarized remodelling of cell junctions and tissue extension. The E-cadherin distribution is also planar polarized and complementary to the Myosin-II distribution. Here we show that E-cadherin polarity is controlled by the polarized regulation of clathrin- and dynamin-mediated endocytosis. Blocking E-cadherin endocytosis resulted in cell intercalation defects. We delineate a pathway that controls the initiation of E-cadherin endocytosis through the regulation of AP2 and clathrin coat recruitment by E-cadherin. This requires the concerted action of the formin Diaphanous (Dia) and Myosin-II. Their activity is controlled by the guanine exchange factor RhoGEF2, which is planar polarized and absent in non-intercalating regions. Finally, we provide evidence that Dia and Myo-II control the initiation of E-cadherin endocytosis by regulating the lateral clustering of E-cadherin.

Epithelial cell division – multiplying without losing touch

“…Finally, the decrease in E-cadherin staining could be due to its localized endocytosis within the ingressing membrane. In support of this latter hypothesis, endocytosis of E-cadherin has been shown to occur in mitotic cells (Bauer et al, 1998) and, in Drosophila, found to be initiated through activation of RhoGEF2, the formin protein Diaphanous and ROCK (Levayer et al, 2011), all of which are localized in the contractile ring.…”

Polarized Rac-dependent protrusions drive epithelial intercalation in the embryonic epidermis of C. elegans

“…During intercalation of the Drosophila germband, for example, actin, nonmuscle myosin II and its regulators accumulate at shrinking junctions, whereas cadherin is enriched at junctions that persist during intercalation (Blankenship et al, 2006;Levayer et al, 2011;Simões et al, 2010;Zallen and Wieschaus, 2004). Asymmetric localization of proteins in epithelial cells that use basolateral protrusive activity during rearrangement has not previously been examined.…”

Coronin 1B supports RhoA signaling at cell-cell junctions through Myosin II

“…7 RhoA signaling is a master regulator of actomyosin cytoskeleton and thus has been implicated in a variety of morphogenetic processes. [31][32][33][34][35][36] While the role for active RhoA signaling in facilitating essential cellular processes has been wellestablished 9,[37][38][39][40][41] there are circumstances where RhoA signaling must be downregulated, either physiologically or pathologically to elicit a biological response. 41,42 Given the importance of the actomyosin cytoskeleton in positively regulating RhoA signaling, 7,[43][44][45] targeting actin-regulators such as Coronin 1B might be one of the approaches to achieve a precise spatiotemporal regulation of RhoA.…”