dOCRL maintains immune cell quiescence by regulating endosomal traffic.

DSpace Repository

Show simple item record

dc.contributor.author Del Signore, Steven J
dc.contributor.author Biber, Sarah A
dc.contributor.author Lehmann, Katherine S
dc.contributor.author Heimler, Stephanie R
dc.contributor.author Rosenfeld, Benjamin H
dc.contributor.author Eskin, Tania L
dc.contributor.author Sweeney, Sean T
dc.contributor.author Rodal, Avital A
dc.date.accessioned 2019-01-29T18:18:26Z
dc.date.available 2019-01-29T18:18:26Z
dc.date.issued 2017
dc.identifier.issn 1553-7404
dc.identifier.other PMC5656325
dc.identifier.uri https://hdl.handle.net/10192/36378
dc.description.abstract Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system. Among many cell biological defects that we identified in docrl mutant hemocytes, we pinpointed the cause of innate immune cell activation to reduced Rab11-dependent recycling traffic and concomitantly increased Rab7-dependent late endosome traffic. Loss of docrl amplifies multiple immune-relevant signals, including Toll, Jun kinase, and STAT, and leads to Rab11-sensitive mis-sorting and excessive secretion of the Toll ligand Spí«tzle. Thus, docrl regulation of endosomal traffic maintains hemocytes in a poised, but quiescent state, suggesting mechanisms by which endosomal misregulation of signaling may contribute to symptoms of Lowe syndrome.
dc.format.extent 1 file
dc.language English
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.isversionof https://dx.doi.org/10.1371/journal.pgen.1007052
dc.rights Creative Commons Attribution 4.0 International License
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject Animals
dc.subject Cytokinesis
dc.subject Drosophila
dc.subject Endosomes
dc.subject Hemocytes
dc.subject Humans
dc.subject Immunity, Innate
dc.subject Mutation
dc.subject Oculocerebrorenal Syndrome
dc.subject Phosphoric Monoester Hydrolases
dc.subject Protein Binding
dc.subject Phosphoric Monoester Hydrolases
dc.subject OCRL protein, human
dc.title dOCRL maintains immune cell quiescence by regulating endosomal traffic.
dc.type Article
dc.contributor.department Department of Biology
dc.relation.journal PLoS Genetics
dc.identifier.pmid 29028801


Files in this item

This item appears in the following Collection(s)

Show simple item record

Creative Commons Attribution 4.0 International License Except where otherwise noted, this item's license is described as Creative Commons Attribution 4.0 International License

Search BIR


Browse

My Account