title: The Rap1-Rgl-Ral signaling network regulates neuroblast cortical polarity and spindle orientation.
abstract: A crucial first step in asymmetric cell division is to establish an axis of cell polarity along which the mitotic spindle aligns. Drosophila melanogaster neural stem cells, called neuroblasts (NBs), divide asymmetrically through intrinsic polarity cues, which regulate spindle orientation and cortical polarity. In this paper, we show that the Ras-like small guanosine triphosphatase Rap1 signals through the Ral guanine nucleotide exchange factor Rgl and the PDZ protein Canoe (Cno; AF-6/Afadin in vertebrates) to modulate the NB division axis and its apicobasal cortical polarity. Rap1 is slightly enriched at the apical pole of metaphase/anaphase NBs and was found in a complex with atypical protein kinase C and Par6 in vivo. Loss of function and gain of function of Rap1, Rgl, and Ral proteins disrupt the mitotic axis orientation, the localization of Cno and Mushroom body defect, and the localization of cell fate determinants. We propose that the Rap1-Rgl-Ral signaling network is a novel mechanism that cooperates with other intrinsic polarity cues to modulate asymmetric NB division.
authors.affiliation: Instituto de Neurociencias de Alicante, Centro Superior de Investigaciones Científicas/Universidad Miguel Hernández, 03550 Alicante, Spain. acarmena@umh.es
authors.forename: Ana
authors.initials: A
authors.lastname: Carmena
authors.forename: Aljona
authors.initials: A
authors.lastname: Makarova
authors.forename: Stephan
authors.initials: S
authors.lastname: Speicher
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism; D005260:Female; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000378:metabolism*; D020726:ral Guanine Nucleotide Exchange Factor / Q000378:metabolism*; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020726:ral Guanine Nucleotide Exchange Factor; D020725:ral GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins
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