title: The PDZ protein Canoe regulates the asymmetric division of Drosophila neuroblasts and muscle progenitors.
abstract: Asymmetric cell division is a conserved mechanism to generate cellular diversity during animal development and a key process in cancer and stem cell biology. Despite the increasing number of proteins characterized, the complex network of proteins interactions established during asymmetric cell division is still poorly understood. This suggests that additional components must be contributing to orchestrate all the events underlying this tightly modulated process. The PDZ protein Canoe (Cno) and its mammalian counterparts AF-6 and Afadin are critical to regulate intracellular signaling and to organize cell junctions throughout development. Here, we show that Cno functions as a new effector of the apical proteins Inscuteable (Insc)-Partner of Inscuteable (Pins)-Galphai during the asymmetric division of Drosophila neuroblasts (NBs). Cno localizes apically in metaphase NBs and coimmunoprecipitates with Pins in vivo. Furthermore, Cno functionally interacts with the apical proteins Insc, Galphai, and Mushroom body defect (Mud) to generate correct neuronal lineages. Failures in muscle and heart lineages are also detected in cno mutant embryos. Our results strongly support a new function for Cno regulating key processes during asymmetric NB division: the localization of cell-fate determinants, the orientation of the mitotic spindle, and the generation of unequal-sized daughter cells.
authors.affiliation: Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas/University Miguel Hernandez, Sant Joan d'Alacant, 03550 Alicante, Spain.
authors.forename: Stephan
authors.initials: S
authors.lastname: Speicher
authors.forename: Anja
authors.initials: A
authors.lastname: Fischer
authors.forename: Juergen
authors.initials: J
authors.lastname: Knoblich
authors.forename: Ana
authors.initials: A
authors.lastname: Carmena
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology*; D019070:Cell Lineage; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006321:Heart / Q000196:embryology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D024510:Muscle Development / Q000502:physiology; D009132:Muscles / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D054731:PDZ Domains; D008941:Spindle Apparatus / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C411670:Mud protein, Drosophila; D009419:Nerve Tissue Proteins; C405164:Pins protein, Drosophila; C400774:baz protein, Drosophila; C092747:cno protein, Drosophila; C098678:insc protein, Drosophila; D019206:GTP-Binding Protein alpha Subunits, Gi-Go