TY - JOUR
T1 - Protein phosphatase 4 coordinates glial membrane recruitment and phagocytic clearance of degenerating axons in Drosophila
AU - Winfree, Lilly M.
AU - Speese, Sean D.
AU - Logan, Mary A.
N1 - Funding Information:
Acknowledgements. We thank the Bloomington Drosophila Stock Center at the Indiana University, the Vienna Drosophila Resource Center, FlyORF at the University of Zurich, Marc Freeman, and Greg Bashaw for flies, and the Developmental Studies Hybridoma Bank at the University of Iowa for antibodies. We also thank Bill Chia for the kind gift of Falafel antibody and flies. This work was supported by the National Institutes of Health (NIH) Grant R01 NS079387-01 (to MAL), NIH New Faculty Recruitment Grant P30NS069346, the Medical Research Foundation of Oregon (to SDS and MAL), the Fred W Fields Foundation (to SDS and MAL), and the Ken and Ginger Harrison Scholar Award in Neuroscience Research (to MAL).
Publisher Copyright:
© The Author(s) 2017.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.1038/cddis.2017.40
DO - 10.1038/cddis.2017.40
M3 - Article
C2 - 28230857
AN - SCOPUS:85029212667
SN - 2041-4889
VL - 8
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 2
M1 - e2623
ER -