The Drosophila CD2AP/CIN85 orthologue Cindr regulates junctions and cytoskeleton dynamics during tissue patterning

Abstract

Developing tissues require cells to undergo intricate processes to shift into appropriate niches. This requires a functional connection between adhesion-mediating events at the cell surface and a cytoskeletal reorganization to permit directed movement. A small number of proteins are proposed to link these processes. Here, we identify one candidate, Cindr, the sole Drosophila melanogaster member of the CD2AP/CIN85 family (this family has been previously implicated in a variety of processes). Using D. melanogaster retina, we demonstrate that Cindr links cell surface junctions (E-cadherin) and adhesion (Roughest) with multiple components of the actin cytoskeleton. Reducing cindr activity leads to defects in local cell movement and, consequently, tissue patterning and cell death. Cindr activity is required for normal localization of Drosophila E-cadherin and Roughest, and we show additional physical and functional links to multiple components of the actin cytoskeleton, including the actin-capping proteins capping protein alpha and capping protein beta. Together, these data demonstrate that Cindr is involved in dynamic cell rearrangement in an emerging epithelium.

The Rac1 hypervariable region in targeting and signaling

“…These findings are in line with the role of CD2AP in podocytes and are in good agreement with findings in Drosophila, where the CD2AP ortholog Cindr promotes E-cadherin localization to junctions and stimulates junctional stability. 64 CD2AP may, in conjunction with Rac1 activity, induce actin rearrangements, as CD2AP binds to the actin capping proteins CapZ and the cortical actin regulator cortactin. 58,59 In fact, we could show that CD2AP links Rac1 to CapZ and cortactin.…”

The vav oncogene antagonises EGFR signalling and regulates adherens junction dynamics during Drosophila eye development

“…Extra primary cells can also be caused by defective cell movements (Johnson et al, 2008;Johnson and Cagan, 2009). To determine whether cell-cell junction stability or adhesion could be affected in vav retinas, we assessed the ommatidial mis-patterning score (OMS), a means of scoring a broad range of specific traits (Johnson and Cagan, 2009).…”

“…Several adhesion molecules such as N-Cadherin (Hayashi and Carthew, 2004), DE-Cadherin (Grzeschik and Knust, 2005) and proteins from the Nephrin and Neph1 families (Bao and Cagan, 2005) have been implicated in these cell-sorting processes to regulate accessory cell numbers, shapes and positions. Some regulators of cell-cell junctions in the retina have been identified, such as the CIN85 and CD2AP orthologue Cindr, an adaptor protein that assembles complexes, required to link cell surface adhesion molecules and the actin cytoskeleton to allow cell shape changes (Johnson et al, 2008). However, the mechanisms by which cell-cell junctions are stabilised while allowing cell movements remains elusive, and the identification of new regulators of junction dynamics will help our understanding of how tissue development is achieved.…”

Comparative study of expression of adaptor proteins Ruk/CIN85 and CD2AP/CMS in normal andtumor human uterus tissues

“…CD2AP/CMS is required for rapid activation of PI3K and ERK/MAPK pathways by TGF-β [29]. Direct interactions between CD2AP/CMS, nephrin, and podocin, and between CD2AP/CMS and the podocyte-specific actin-bundling protein synaptopodin, are essential for slit diaphragm integrity [16]. CD2AP/CMS was shown to localize in highly dynamic actin structures at the leading edge of cells and membrane ruffles, and have a role in cytoskeleton polarization associated with the activation of T cell receptors [10].…”