title: Ack kinase regulates CTP synthase filaments during Drosophila oogenesis.
abstract: The enzyme CTP synthase (CTPS) dynamically assembles into macromolecular filaments in bacteria, yeast, Drosophila, and mammalian cells, but the role of this morphological reorganization in regulating CTPS activity is controversial. During Drosophila oogenesis, CTPS filaments are transiently apparent in ovarian germline cells during a period of intense genomic endoreplication and stockpiling of ribosomal RNA. Here, we demonstrate that CTPS filaments are catalytically active and that their assembly is regulated by the non-receptor tyrosine kinase DAck, the Drosophila homologue of mammalian Ack1 (activated cdc42-associated kinase 1), which we find also localizes to CTPS filaments. Egg chambers from flies deficient in DAck or lacking DAck catalytic activity exhibit disrupted CTPS filament architecture and morphological defects that correlate with reduced fertility. Furthermore, ovaries from these flies exhibit reduced levels of total RNA, suggesting that DAck may regulate CTP synthase activity. These findings highlight an unexpected function for DAck and provide insight into a novel pathway for the developmental control of an essential metabolic pathway governing nucleotide biosynthesis.
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA Todd.Strochlic@drexelmed.edu Alana.OReilly@fccc.edu jeffrey.peterson@fccc.edu.
authors.forename: Todd I
authors.initials: TI
authors.lastname: Strochlic
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA Epigenetics and Progenitor Cells Keystone Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Stavrides
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Sam V
authors.initials: SV
authors.lastname: Thomas
authors.affiliation: Genomics Core Facility, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Nicolas
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA Epigenetics and Progenitor Cells Keystone Program, Fox Chase Cancer Center, Philadelphia, PA, USA Todd.Strochlic@drexelmed.edu Alana.OReilly@fccc.edu jeffrey.peterson@fccc.edu.
authors.forename: Alana M
authors.initials: AM
authors.lastname: O'Reilly
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA Todd.Strochlic@drexelmed.edu Alana.OReilly@fccc.edu jeffrey.peterson@fccc.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Peterson
mesh_terms: D000818:Animals; D019731:Carbon-Nitrogen Ligases / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D009866:Oogenesis; D010053:Ovary / Q000378:metabolism; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D012313:RNA; C498593:Ack protein, Drosophila; D011505:Protein-Tyrosine Kinases; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase
keywords: Ack; CTP synthase; Drosophila oogenesis; cytoophidia