title: Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signaling and cell growth during Drosophila development.
abstract: During development, Drosophila larvae undergo a dramatic increase in body mass wherein nutritional and developmental cues are transduced into growth through the activity of complex signaling pathways. Class I phosphoinositide 3-kinases have an established role in this process. In this study we identify Drosophila phosphatidylinositol 5-phosphate 4-kinase (dPIP4K) as a phosphoinositide kinase that regulates growth during larval development. Loss-of-function mutants in dPIP4K show reduced body weight and prolonged larval development, whereas overexpression of dPIP4K results both in an increase in body weight and shortening of larval development. The growth defect associated with dPIP4K loss of function is accompanied by a reduction in the average cell size of larval endoreplicative tissues. Our findings reveal that these phenotypes are underpinned by changes in the signaling input into the target of rapamycin (TOR) signaling complex and changes in the activity of its direct downstream target p70 S6 kinase. Together, these results define dPIP4K activity as a regulator of cell growth and TOR signaling during larval development.
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Gandhi Krishi Vignana Kendra Campus, Bangalore 560065, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Gupta
authors.forename: Sarah
authors.initials: S
authors.lastname: Toscano
authors.forename: Deepti
authors.initials: D
authors.lastname: Trivedi
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: Swarna
authors.initials: S
authors.lastname: Mathre
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Clarke
authors.forename: Nullin
authors.initials: N
authors.lastname: Divecha
authors.forename: Padinjat
authors.initials: P
authors.lastname: Raghu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000201:enzymology / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018613:Microscopy, Confocal; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor); C416303:target of rapamycin protein, Drosophila; C402182:phosphatidylinositol phosphate 4-kinase; D058570:TOR Serine-Threonine Kinases