RT info:eu-repo/semantics/article T1 Grasshopper Lazarillo, a GPI-anchored Lipocalin, increases Drosophila longevity and stress resistance, and functionally replaces its secreted homolog NLaz A1 Ruiz, Mario A1 Wicker-Thomas, Claude A1 Sánchez Romero, Diego A1 Ganfornina Álvarez, María Dolores K1 Lipocainas K1 Células gliales K1 Insectos AB Lazarillo (Laz) is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein first characterized in thedeveloping nervous system of the grasshopper Schistocerca americana. It belongs to the Lipocalins,a functionally diverse family of mostly secreted proteins. In this work we test whether the protectivecapacity known for Laz homologs in flies and vertebrates (NLaz, GLaz and ApoD) is evolutionarilyconserved in grasshopper Laz, and can be exerted from the plasma membrane in a cell-autonomousmanner. First we demonstrate that extracellular forms of Laz have autocrine and paracrine protectingeffects for oxidative stress-challenged Drosophila S2 cells. Then we assay the effects of overexpressingGPI-linked Laz in adult Drosophila and whether it rescues both known and novel phenotypes of NLaz nullmutants. Local effects of GPI-linked Laz inside and outside the nervous system promote survival upondifferent stress forms, and extend lifespan and healthspan of the flies in a cell-type dependent manner.Outside the nervous system, expression in fat body cells but not in hemocytes results in protection.Within the nervous system, glial cell expression is more effective than neuronal expression. Laz actionsare sexually dimorphic in some expression domains. Fat storage promotion and not modifications inhydrocarbon profiles or quantities explain the starvationedesiccation resistance caused by Laz overexpression.This effect is exerted when Laz is expressed ubiquitously or in dopaminergic cells, but not inhemocytes. Grasshopper Laz functionally restores the loss of NLaz, rescuing stress-sensitivity as well aspremature accumulation of aging-related damage, monitored by advanced glycation end products(AGEs). However Laz does not rescue NLaz courtship behavioral defects. Finally, the presence of two newLipocalins with predicted GPI-anchors in mosquitoes shows that the functional advantages ofGPI-linkage have been commonly exploited by Lipocalins in the arthropodan lineage. PB Elsevier SN 0965-1748 YR 2012 FD 2012 LK http://uvadoc.uva.es/handle/10324/6092 UL http://uvadoc.uva.es/handle/10324/6092 LA eng NO Insect Biochemistry and Molecular Biology, 2012, vol. 42, p. 776-789 NO Producción Científica DS UVaDOC RD 19-abr-2024