title: Slimming down fat makes neuropathic hippo: the Fat/Hippo tumor suppressor pathway protects adult neurons through regulation of autophagy.
abstract: Polyglutamine diseases are accompanied by large-scale alterations of transcription that may be responsible for neurodegeneration. We have monitored early transcriptional alterations in a Drosophila model for dentatorubral-pallidoluysian atrophy (DRPLA) and reported the critical downregulation of the fat tumor suppressor gene. We show that, besides partially mediating neurodegeneration in the Drosophila model for DRPLA, fat and the downstream hippo pathway are essential for adult neuronal homeostasis. This function of the Fat/Hippo pathway is independent of the well-established actions on proliferation and cell polarity; rather it has an impact upon autophagy, which is blocked and ineffective in fat/hippo mutants. These findings reveal the unexpected role in postmitotic neuronal homeostasis of a tumor suppressor pathway and hint at a new player involved directly or indirectly in the regulation of autophagy.
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, Guy's Campus, London, UK.
authors.forename: Piera
authors.initials: P
authors.lastname: Calamita
authors.forename: Manolis
authors.initials: M
authors.lastname: Fanto
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001343:Autophagy; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019610:Cytoprotection; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008954:Models, Biological; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000099317:Hippo Kinases
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C472307:ft protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases