Retromer promotes immune quiescence by suppressing Spatzle-Toll pathway in Drosophila

UMMS Affiliation

Program in Molecular Medicine

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Cellular and Molecular Physiology | Hemic and Immune Systems | Immunity | Translational Medical Research


The Toll and Toll-like receptor signaling pathways are evolutionarily conserved pathways that regulate innate immunity in insects and mammals. While efforts have been made to clarify the signal transduction events that occur during infection, much less is known about the components that maintain immune quiescence. Here we show that retromer, an intracellular protein complex known for regulating vesicle trafficking, functions in modulating the Toll pathway in Drosophila melanogaster. In mutant animals lacking retromer function, the Toll pathway but not JAK-STAT or IMD pathway is activated, triggering both cellular and humoral responses. Genetic epistasis and clonal analysis suggest that retromer regulates a component that acts upstream of Toll. Our data further show that in the mutant the Toll ligand Spatzle has a processing pattern similar to that of after infection. Together, the results suggest a novel function of retromer in regulating Toll pathway and innate immunity at a step that modulates ligand processing or activity.


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DOI of Published Version



J Cell Physiol. 2014 Apr;229(4):512-520. doi: 10.1002/jcp.24472. Link to article on publisher's site

Journal/Book/Conference Title

Journal of cellular physiology

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Link to Article in PubMed

PubMed ID