Ligand binding-dependent functions of the lipocalin NLaz: an in vivo study in Drosophila

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Mario RuizD Sánchez

Abstract

Lipocalins are small extracellular proteins mostly described as lipid carriers. The Drosophila lipocalin NLaz (neural Lazarillo) modulates the IIS pathway and regulates longevity, stress resistance, and behavior. Here, we test whether a native hydrophobic pocket structure is required for NLaz to perform its functions. We use a point mutation altering the binding pocket (NLaz(L130R)) and control mutations outside NLaz binding pocket. Tryptophan fluorescence titration reveals that NLaz(L130R) loses its ability to bind ergosterol and the pheromone 7(z)-tricosene but retains retinoic acid binding. Using site-directed transgenesis in Drosophila, we test the functionality of the ligand binding-altered lipocalin at the organism level. NLaz-dependent life span reduction, oxidative stress and starvation sensitivity, aging markers accumulation, and deficient courtship are rescued by overexpression of NLaz(WT), but not of NLaz(L130R). Transcriptional responses to aging and oxidative stress show a large set of age-responsive genes dependent on the integrity of NLaz binding pocket. Inhibition of IIS activity and modulation of oxidative stress and infection-responsive genes are binding pocket-dependent processes. Control of energy metabolite...Continue Reading

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Citations

Sep 1, 2015·Ageing Research Reviews·Ekaterina N ProshkinaAlexey A Moskalev
Apr 15, 2015·Experimental Gerontology·Diego SanchezMaria D Ganfornina
May 11, 2016·Archives of Insect Biochemistry and Physiology·André Fernando Ditondo MicasMárcia Maria Gentile Bitondi
May 1, 2021·Genome Biology and Evolution·Jiao ZhuPaolo Pelosi
Sep 5, 2021·Biological Reviews of the Cambridge Philosophical Society·Paolo Pelosi, Wolfgang Knoll

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