Your browser doesn't support javascript.
loading
Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development.
Medina-Yáñez, Ignacio; Olivares, Gonzalo H; Vega-Macaya, Franco; Mlodzik, Marek; Olguín, Patricio.
Afiliação
  • Medina-Yáñez I; Program of Human Genetics, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • Olivares GH; Biomedical Neuroscience Institute, Department of Neuroscience, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • Vega-Macaya F; Program of Human Genetics, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • Mlodzik M; Biomedical Neuroscience Institute, Department of Neuroscience, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • Olguín P; Program of Human Genetics, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Sci Rep ; 10(1): 21731, 2020 12 10.
Article em En | MEDLINE | ID: mdl-33303974
Organ cell diversity depends on binary cell-fate decisions mediated by the Notch signalling pathway during development and tissue homeostasis. A clear example is the series of binary cell-fate decisions that take place during asymmetric cell divisions that give rise to the sensory organs of Drosophila melanogaster. The regulated trafficking of Sanpodo, a transmembrane protein that potentiates receptor activity, plays a pivotal role in this process. Membrane lipids can regulate many signalling pathways by affecting receptor and ligand trafficking. It remains unknown, however, whether phosphatidic acid regulates Notch-mediated binary cell-fate decisions during asymmetric cell divisions, and what are the cellular mechanisms involved. Here we show that increased phosphatidic acid derived from Phospholipase D leads to defects in binary cell-fate decisions that are compatible with ectopic Notch activation in precursor cells, where it is normally inactive. Null mutants of numb or the α-subunit of Adaptor Protein complex-2 enhance dominantly this phenotype while removing a copy of Notch or sanpodo suppresses it. In vivo analyses show that Sanpodo localization decreases at acidic compartments, associated with increased internalization of Notch. We propose that Phospholipase D-derived phosphatidic acid promotes ectopic Notch signalling by increasing receptor endocytosis and inhibiting Sanpodo trafficking towards acidic endosomes.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Fosfatídicos / Transdução de Sinais / Transporte Proteico / Proteínas de Drosophila / Organogênese / Drosophila / Receptores Notch / Mecanorreceptores Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Fosfatídicos / Transdução de Sinais / Transporte Proteico / Proteínas de Drosophila / Organogênese / Drosophila / Receptores Notch / Mecanorreceptores Idioma: En Ano de publicação: 2020 Tipo de documento: Article