Recombinant Mouse VLDLR (Cys297) Protein, CF

VLDL R is a 130 kDa type I transmembrane protein in the LDL receptor family that plays a significant role in lipid metabolism and in nervous system development and function (1, 2). Mouse VLDL R has a 774 aa extracellular domain (ECD) (aa 25 ‑ 798) and a 54 aa cytoplasmic domain. The ECD contains eight LDLR class A repeats, three EGF‑like domains, six LDLR class B repeats, and a juxtamembrane region that is rich in O‑linked glycosylation (3, 4, 5). The cytoplasmic domain contains one NPXY internalization motif. Mouse VLDL R has at least one 105 kDa alternative splice form. This variant (termed type II VLDL R) shows an Arg substitution for aa 751 ‑ 779, and has been associated with endothelial cells (5, 6). The VLDL R expressed here corresponds to a polymorphic form that shows a Cys at position 297 of the precursor. This generates a disulfide bond in the 7^th LDL class A domain that is not present when position 297 is occupied by Ser (SwissProt # P98156). The 7^th domain is suggested to be a critical determinant of apoE binding to VLDL R (7). VLDL R is predominantly expressed in striated muscle, adipose tissue, brain, and endothelial cells lining capillaries and small arterioles (3, 4, 8, 9). VLDL R participates in the tissue uptake of fatty acids from plasma by mediating the internalization of ApoE‑containing lipoparticles (i.e. VLDL, beta‑VLDL, and chylomicron remnants) (8, 10). VLDL R binds and internalizes lipoprotein lipase (LPL) and mediates its transport from the basolateral to the lumenal face of endothelial cells (9, 11). VLDL R knockout mice are characterized by reduced LPL activity, reduced serum triglyceride clearance, and a resistance to developing obesity (10, 12, 13). VLDL R influences breast cancer cell motility by mediating the uptake of uPAR‑PAI1 complexes (9, 14). Lipoprotein accumulation via macrophage VLDL R is instrumental in promoting the formation of atherosclerotic plaques (15). In the nervous system, VLDL R and ApoE R2 interactions with reelin are critical for neuronal migration and positioning in the developing brain (16). VLDL R also functions in adult hippocampal synapse maturation, synaptic plasticity, and memory formation (17, 18). The ECD of mouse VLDL R shares 95% aa sequence identity with human and rat VLDL R. Within shared regions, mouse VLDL R shares 55% and 53% aa sequence identity with ApoE R2 and LDL R, respectively.