Apolipoprotein D

Abstract

ApoD is a 25 to 30 kDa glycosylated protein, member of the lipocalin superfamily. As a transporter of several small hydrophobic molecules, its known biological functions are mostly associated to lipid metabolism and neuroprotection. ApoD is a multi-ligand, multi-function protein that is involved lipid trafficking, food intake, inflammation, antioxidative response and development and in different types of cancers. An important aspect of ApoD's role in lipid metabolism appears to involve the transport of arachidonic acid, and the modulation of eicosanoid production and delivery in metabolic tissues. ApoD expression in metabolic tissues has been associated positively and negatively with insulin sensitivity and glucose homeostasis in a tissue dependent manner. ApoD levels rise considerably in association with aging and neuropathologies such as Alzheimer's disease, stroke, meningoencephalitis, moto-neuron disease, multiple sclerosis, schizophrenia and Parkinson's disease. ApoD is also modulated in several animal models of nervous system injury/pathology.

Keywords: Apolipoprotein D; Arachidonic acid; Lipid metabolism; Lipid transport; Lipocalin; Neuroprotection.

Fig. 1.. Structure of human ApoD in complex with progesterone

(adapted from Eichinger et al., 2007). Left: front view showing the 8 anti-parallel β-strands (yellow) structure forming the hydrophobic cavity typical of the lipocalins. Loops A/B, C/D, E/F and G/H link the β-strands at the open end of the protein. Other loops are present at the opposite end of the protein (white). There are 2 α-helix (purple) located close to the cavity, one of which is able to close the cavity. The two glycosylated residues (N45 and N78) are shown. The 2 disulfide bridges are not visible. Right: top view of the cavity showing the progesterone ligand (grey). Loops A/B, E/F and G/H are rich in hydrophobic residues and very likely enable the protein to interact with HDL and with membranes. For details, see Eichinger et al., 2007.

Fig. 2.. Relative ApoD mRNA and protein expression in tissues of different species.

ApoD expression in the figure is an average value from the literature. ApoD expression in a tissue is expressed as a percentage of the strongest ApoD tissue expression for that species. Tissue expression between different species should not be compared as they are only relative to their own species. Tissues in which ApoD was detected but not quantified are noted in yellow. Expression data were obtained from multiple sources: Human (Uhlen et al. 2015) data available at https://www.proteinatlas.org/ENSG00000189058-APOD/tissue, (Fishilevich et al. 2016; Ben-Ari Fuchs et al. 2016) data available at https://www.genecards.org/cgi-bin/carddisp.pl?gene=APOD, (Séguin et al.,1995; Drayna et al. 1986); Rhesus (Smith et alo., 1990); Rabbit (Provost et al. 1990); Mouse (Séguin et al., 1995; Do Carmo et al. 2009a; Li et al. 2016; Cofer and Ross 1996); Rat (Séguin, Desforges, and Rassart 1995; Boyles et al., 1990b); Guinea pig (Provost et al. 1995); Chicken (Ganfornina et al. 2005).