title: Mutational analysis supports a core role for Drosophila α-catenin in adherens junction function.
abstract: α-catenin associates the cadherin-catenin complex with the actin cytoskeleton. α-catenin binds to β-catenin, which links it to the cadherin cytoplasmic tail, and F-actin, but also to a multitude of actin-associated proteins. These interactions suggest a highly complex cadherin-actin interface. Moreover, mammalian αE-catenin has been implicated in a cadherin-independent cytoplasmic function in Arp2/3-dependent actin regulation, and in cell signaling. The function and regulation of individual molecular interactions of α-catenin, in particular during development, are not well understood. We have generated mutations in Drosophila α-Catenin (α-Cat) to investigate α-Catenin function in this model, and to establish a setup for testing α-Catenin-related constructs in α-Cat-null mutant cells in vivo. Our analysis of α-Cat mutants in embryogenesis, imaginal discs and oogenesis reveals defects consistent with a loss of cadherin function. Compromising components of the Arp2/3 complex or its regulator SCAR ameliorate the α-Cat loss-of-function phenotype in embryos but not in ovaries, suggesting negative regulatory interactions between α-Catenin and the Arp2/3 complex in some tissues. We also show that the α-Cat mutant phenotype can be rescued by the expression of a DE-cadherin::α-Catenin fusion protein, which argues against an essential cytosolic, cadherin-independent role of Drosophila α-Catenin.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ritu
authors.initials: R
authors.lastname: Sarpal
authors.forename: Milena
authors.initials: M
authors.lastname: Pellikka
authors.forename: Ridhdhi R
authors.initials: RR
authors.lastname: Patel
authors.forename: Felix Yan Wai
authors.initials: FY
authors.lastname: Hui
authors.forename: Dorothea
authors.initials: D
authors.lastname: Godt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Tepass
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism; D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006257:Head / Q000254:growth & development; D060227:Imaginal Discs / Q000378:metabolism; D007814:Larva / Q000254:growth & development; D008297:Male; D016296:Mutagenesis; D009866:Oogenesis / Q000235:genetics; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D013049:Spectrin / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015053:Zygote / Q000378:metabolism; D051178:alpha Catenin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
chemical_list: C495305:ARM protein, Drosophila; D051376:Actin-Related Protein 2-3 Complex; D051186:Armadillo Domain Proteins; D015820:Cadherins; D029721:Drosophila Proteins; D014157:Transcription Factors; D051178:alpha Catenin; D013049:Spectrin