title: Protein phosphatase 4 coordinates glial membrane recruitment and phagocytic clearance of degenerating axons in Drosophila.
abstract: Neuronal damage induced by injury, stroke, or neurodegenerative disease elicits swift immune responses from glial cells, including altered gene expression, directed migration to injury sites, and glial clearance of damaged neurons through phagocytic engulfment. Collectively, these responses hinder further cellular damage, but the mechanisms that underlie these important protective glial reactions are still unclear. Here, we show that the evolutionarily conserved trimeric protein phosphatase 4 (PP4) serine/threonine phosphatase complex is a novel set of factors required for proper glial responses to nerve injury in the adult Drosophila brain. Glial-specific knockdown of PP4 results in reduced recruitment of glia to severed axons and delayed glial clearance of degenerating axonal debris. We show that PP4 functions downstream of the the glial engulfment receptor Draper to drive glial morphogenesis through the guanine nucleotide exchange factor SOS and the Rho GTPase Rac1, revealing that PP4 molecularly couples Draper to Rac1-mediated cytoskeletal remodeling to ensure glial infiltration of injury sites and timely removal of damaged neurons from the CNS.
authors.affiliation: Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Lilly M
authors.initials: LM
authors.lastname: Winfree
authors.affiliation: Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Speese
authors.affiliation: Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Logan
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4