Lipocalin-interacting-membrane-receptor (LIMR) mediates cellular internalization of β-lactoglobulin

Abstract

beta-Lactoglobulin (BLG) is a member of the lipocalin protein family and a major food-borne allergen in humans. Numerous in vitro studies have suggested a role for BLG in molecular transport processes; however, its physiological role remains enigmatic. A cellular receptor for BLG has been proposed, but has not yet been identified. Here we show that human LIMR, known to act as an endocytic receptor for lipocalin-1, also binds bovine BLG and mediates its cellular uptake. The specificity of this interaction is corroborated by a complete block of cellular uptake of BLG in the presence of LIMR antibodies or LIMR downregulation by antisense RNA. Furthermore, heterologous expression of human LIMR in insect cells mediates cellular internalization of FITC-BLG. Since LIMR is highly expressed in the human intestine, it might also function in the uptake of food-borne BLG.

Model based optimization of feeding regimens in aquaculture: Application to the improvement of Octopus vulgaris viability in captivity

“…According to Lee (1994), cephalopod metabolism is mainly protein and amino acid driven, so total protein content and amino acids composition are key factors in the design of artificial diets for these species. On the other hand, the importance of lipids for cephalopod nutrition, related with brain and visual system development as well as cell membrane composition especially during early development, has been shown (Domingues et al, 2003(Domingues et al, , 2004Fluckinger et al, 2008;Koueta et al, 2002;Navarro and Villanueva, 2000;Perrin et al, 2004;Sinanoglou and Miniadis-Meimaroglou, 2000;Sykes et al, 2006Sykes et al, , 2009. Some conclusions, with relevance for the present study, can be drawn from the text above.…”

The tinker, tailor, soldier in intracellular B12 trafficking

“…Genetic defects in the LMBRD1 gene affect both the cytosolic and mitochondrial branches of cobalamin metabolism. LIMR internalizes cargo bound to tear lipocalin [16] and to β-lactoglobulin [17], which binds the tetrapyrrole, protoporphyrin IX. This leads to the hypothesis that an additional protein might be required to bind free lysosomal B 12 for delivery to the exporter, LMBD1 [15 •• ].…”

LMBRD1: the gene for the cblF defect of vitamin B12 metabolism

“…Lipocalins are small secreted proteins that bind and carry hydrophobic molecules in biological fluids (Flower 1996). LIMR is a cell-surface receptor that internalizes two lipocalins-tear lipocalin and β-lactoglobulin (Fluckinger et al 2008;Wojnar et al 2003)-a lipocalin that also binds protoporphyrin IX (Dufour et al 1990). …”