Lipid-binding properties of human ApoD and Lazarillo-related lipocalins: functional implications for cell differentiation
Language: 
English
Short Title: 
Lipid-binding properties of human ApoD and Lazarillo-related lipocalins
Abstract: 

Lipocalins are a family of proteins characterized by a conserved eight-stranded ?-barrel structure with a ligand-binding pocket. They perform a wide range of biological functions and this functional multiplicity must relate to the lipid partner involved. Apolipoprotein D (ApoD) and its insect homologues, Lazarillo (Laz) and neural Lazarillo (NLaz), share common ancestral functions like longevity, stress resistance and lipid metabolism regulation, coexisting with very specialized functions, like courtship behavior. Using tryptophan fluorescence titration, we screened the binding of 15 potential lipid partners for NLaz, ApoD and Laz and uncovered several novel ligands with apparent dissociation constants in the low micromolar range. Retinoic acid (RA), retinol, fatty acids and sphingomyelin are shared ligands. Sterols, however, showed a species-specific binding pattern: cholesterol did not show strong binding to human ApoD, whereas NLaz and Laz did bind ergosterol. Among the lipocalin-specific ligands, we found that ApoD selectively binds the endocannabinoid anandamide but not 2-acylglycerol, and that NLaz binds the pheromone 7-tricosene, but not 7,11-heptacosadiene or 11-cis-vaccenyl acetate. To test the functional relevance of lipocalin ligand binding at the cellular level, we analyzed the effect of ApoD, Laz and NLaz preloaded with RA on neuronal differentiation. Our results show that ApoD is necessary and sufficient to allow for RA differentiating activity. Both human ApoD and Drosophila NLaz successfully deliver RA to immature neurons, driving neurite outgrowth. We conclude that ApoD, NLaz and Laz bind selectively to a different but overlapping set of lipid ligands. This multispecificity can explain their varied physiological functions.

Author(s): 
Ruiz, Mario
Sanchez, Diego
Correnti, Colin
Strong, Roland K.
Ganfornina, Maria D.
Item Type: 
Journal Article
Publication Title: 
The FEBS journal
Journal Abbreviation: 
FEBS J.
Publication Date: 
2013-08
Publication Year: 
2013
Pages: 
3928-3943
Volume: 
280
Issue: 
16
ISSN: 
1742-4658
DOI: 
10.1111/febs.12394
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23777559

Turabian/Chicago Citation

Mario Ruiz, Diego Sanchez, Colin Correnti, Roland K. Strong and Maria D. Ganfornina. 2013-08. "Lipid-binding properties of human ApoD and Lazarillo-related lipocalins: functional implications for cell differentiation." The FEBS journal 280: 16: 3928-3943. 10.1111/febs.12394.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1111/febs.12394 | issn = 1742-4658 | volume = 280 | pages = 3928-3943 | last = Ruiz | first = Mario | coauthors = Sanchez, Diego, Correnti, Colin, Strong, Roland K., Ganfornina, Maria D. | title = Lipid-binding properties of human ApoD and Lazarillo-related lipocalins: functional implications for cell differentiation | journal = The FEBS journal | date = 2013-08 | pmid = | pmc = }} </ref>