Avian apolipoprotein A-V binds to LDL receptor gene family members

Wolfgang J Schneider,Johannes Nimpf,Larry A Cogburn,Andrea Dichlberger

doi:10.1194/jlr.c600026-jlr200

Wolfgang J Schneider, Johannes Nimpf + Show 2 more

Open Access

https://doi.org/10.1194/jlr.c600026-jlr200

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Abstract

Apolipoprotein A-V (apoA-V) affects plasma triglyceride (TG) levels; however, the properties of apoA-V that mediate its action(s) are still incompletely understood. It is unclear how apoA-V, whose plasma concentration is extremely low, can affect the pronounced TG differences observed in individuals with various apoA-V dysfunctions. To gain novel insights into apoA-V biology, we expanded our previous studies in the chicken to this apolipoprotein. First, we characterized the first avian apoA-V, revealing its expression not only in liver and small intestine but also in brain, kidney, and ovarian follicles and showing its presence in the circulation. Second, we demonstrate directly that galline apoA-V binds to the major LDL receptor family member (LR) of the laying hen and that this interaction does not depend on the association of the apolipoprotein with lipid or lipoproteins. We propose that a direct interaction with LRs may represent a novel, additional mechanism for the modulation of TG levels by apoA-V.

Highlights

Apolipoprotein A-V affects plasma triglyceride (TG) levels; the properties of apoA-V that mediate its action(s) are still incompletely understood
We show that i) chickens do synthesize the protein encoded by the avian APOA5 gene; ii) ggapoA-V is detectable in the circulation; and iii) chicken apoA-V interacts with a prominent member of the avian LDL receptor gene family, as determined by direct ligand blotting methodology
We propose that the regulation of the receptor-modulating activity of apoA-V occurs at the level of its distribution in serum and at the site(s) of clearance, parameters that are related to LDL receptor family member (LR) levels, to liver status [1], to apoC-II/ C-III ratios, to the apolipoprotein content at the hepatocyte surface [6, 8], and/or to expression levels of proteoglycans [7]

Summary

Introduction

Apolipoprotein A-V (apoA-V) affects plasma triglyceride (TG) levels; the properties of apoA-V that mediate its action(s) are still incompletely understood. As discussed previously [7], possible functions include proteoglycan-dependent direct modulation of LPL activity, interference with the secretion of nascent TG-rich lipoproteins, and/or indirect effects on lipolysis via apoA-V binding to heparan sulfate proteoglycans. Another possibility for the action of apoA-V has been indicated by the finding [8] that VLDL particles from apoa52/2 mice are poorer competitors for binding to the LDL receptor than those from normal mice, implying a possible role for apoA-V in mediating or modulating lipoprotein receptor binding. We show that i) chickens do synthesize the protein encoded by the avian APOA5 gene (i.e., ggapoA-V); ii) ggapoA-V is detectable in the circulation; and iii) chicken apoA-V interacts with a prominent member of the avian LDL receptor gene family, as determined by direct ligand blotting methodology

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