The Drosophila afadin homologue Canoe regulates linkage of the actin cytoskeleton to adherens junctions during apical constriction

Abstract

Cadherin-based adherens junctions (AJs) mediate cell adhesion and regulate cell shape change. The nectin–afadin complex also localizes to AJs and links to the cytoskeleton. Mammalian afadin has been suggested to be essential for adhesion and polarity establishment, but its mechanism of action is unclear. In contrast, Drosophila melanogaster’s afadin homologue Canoe (Cno) has suggested roles in signal transduction during morphogenesis. We completely removed Cno from embryos, testing these hypotheses. Surprisingly, Cno is not essential for AJ assembly or for AJ maintenance in many tissues. However, morphogenesis is impaired from the start. Apical constriction of mesodermal cells initiates but is not completed. The actomyosin cytoskeleton disconnects from AJs, uncoupling actomyosin constriction and cell shape change. Cno has multiple direct interactions with AJ proteins, but is not a core part of the cadherin–catenin complex. Instead, Cno localizes to AJs by a Rap1- and actin-dependent mechanism. These data suggest that Cno regulates linkage between AJs and the actin cytoskeleton during morphogenesis.

Canoe functions at the CNS midline glia in a complex with Shotgun and Wrapper-Nrx-IV during neuron-glia interactions

“…This suggests that other protein(s) stabilize Cno at this location (see below). (Sawyer et al, 2009). Interestingly, we found that Shg was present at the MG and was highly enriched, as is Cno, at the interface between the MG and commissural axons (Fig.…”

Cadherin controls nectin recruitment into adherens junctions by remodeling the actin cytoskeleton

“…Inhibitors of nectin adhesion or afadin knockdown slow the formation of cadherin adhesive clusters in a Ca 2+ -switch assay (Sato et al, 2006;Lorger and Moelling, 2006) or between two cells upon coming into contact with one another (Indra et al, 2014). However, this defect in the kinetics of adherens junction formation does not affect the general appearance of cell-cell adhesion contacts, including the ultrastructural features of adherens junctions (Zhadanov et al, 1999;Sawyer et al, 2009;Tanaka-Okamoto et al, 2011). Therefore, the available data show that nectin facilitates the formation of adherens junctions, but it is involved neither in the basic mechanisms of their assembly nor in their structural organization.…”

Loss of AF6/afadin, a marker of poor outcome in breast cancer, induces cell migration, invasiveness and tumor growth

“…This includes disorganization of the ectoderm, impaired migration of the mesoderm and loss of somites (Ikeda et al, 1999;Zhadanov et al, 1999). In Drosophila, afadin homolog Canoe (Cno) (Miyamoto et al, 1995) is essential during morphogenesis to maintain adherens junctions by connecting adherens junctions to actin (Sawyer et al, 2009). However, in contrast to mammals, Cno is dispensable for cadherin-catenin-based adherens junctions assembly and establishment of cell polarity in the fly (Sawyer et al, 2009).…”

“…In Drosophila, afadin homolog Canoe (Cno) (Miyamoto et al, 1995) is essential during morphogenesis to maintain adherens junctions by connecting adherens junctions to actin (Sawyer et al, 2009). However, in contrast to mammals, Cno is dispensable for cadherin-catenin-based adherens junctions assembly and establishment of cell polarity in the fly (Sawyer et al, 2009). Cno contributes to regulate signal transduction during morphogenesis and genetically interacts with RAS, JNK, NOTCH and WNT pathways (Miyamoto et al, 1995;Takahashi et al, 1998;Matsuo et al, 1999;Boettner et al, 2003;Carmena et al, 2006).…”