title: Evolutionary conservation of Notch signaling inhibition by TMEM131L overexpression.
abstract: Human KIAA0922/TMEM131L encodes a transmembrane protein, TMEM131L, that regulates the canonical Wnt/β-catenin signaling pathway by eliciting the lysosome-dependent degradation of phosphorylated LRP6 co-receptor. Here, we use a heterospecific Drosophila transgenic model to examine the potential evolutionary conservation of TMEM131L function. Analysis of TMEM131L transgenic flies shows that TMEM131L interference with the Wnt pathway results primarily from a Notch-dependent decrease in Wingless production. Consistently, lentivirus-mediated overexpression of TMEM131L in human CD34+hematopoietic progenitor cells leads to decreased susceptibility to Notch1 ligation and defective commitment toward the T lineage. These results show that TMEM131L corresponds to an evolutionary conserved regulator of the Notch signaling pathway.
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines/Université Paris-Saclay, Ecole Pratique des Hautes Etudes/PSL Research University, Montigny-le-Bretonneux, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Szuplewski
authors.affiliation: INSERM U1126, Ecole Pratique des Hautes Etudes/PSL Research University, Hôpital Saint-Louis, Institut Universitaire d'Hématologie, hôpital Saint-Louis, Paris, France.
authors.forename: Nesrine
authors.initials: N
authors.lastname: Maharzi
authors.affiliation: INSERM U1126, Ecole Pratique des Hautes Etudes/PSL Research University, Hôpital Saint-Louis, Institut Universitaire d'Hématologie, hôpital Saint-Louis, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Nelson
authors.affiliation: INSERM U1126, Ecole Pratique des Hautes Etudes/PSL Research University, Hôpital Saint-Louis, Institut Universitaire d'Hématologie, hôpital Saint-Louis, Paris, France.
authors.forename: Kutaiba
authors.initials: K
authors.lastname: Alhaj Hussen
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines/Université Paris-Saclay, Ecole Pratique des Hautes Etudes/PSL Research University, Montigny-le-Bretonneux, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Mignotte
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines/Université Paris-Saclay, Ecole Pratique des Hautes Etudes/PSL Research University, Montigny-le-Bretonneux, France. Electronic address: isabelle.guenal@uvsq.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guénal
authors.affiliation: INSERM U1126, Ecole Pratique des Hautes Etudes/PSL Research University, Hôpital Saint-Louis, Institut Universitaire d'Hématologie, hôpital Saint-Louis, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Canque
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004330:Drosophila / Q000235:genetics*; D019143:Evolution, Molecular; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051880:Receptors, Notch; D015398:Signal Transduction / Q000235:genetics*; D013045:Species Specificity; D026801:Synteny / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D051880:Receptors, Notch; C582754:TMEM131L protein, human
keywords: Drosophila; Human T cell differentiation; Notch; TMEM131L