The Drosophila CD2AP/CIN85 orthologue Cindr regulates junctions and cytoskeleton dynamics during tissue patterning.
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.
Johnson
Ruth I
RI
Department of Developmental and Regenerative Biology, Mount Sinai Medical School, New York, NY 10029, USA.
Seppa
Midori J
MJ
Cagan
Ross L
RL
D051344:Actin Capping Proteins / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*
D051344:Actin Capping Proteins; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; C528411:Cindr protein, Drosophila; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D008840:Microfilament Proteins; C433810:SH3KBP1 protein, human; C085209:rst protein, Drosophila; C501889:shg protein, Drosophila