scholarly journals Low Density Lipoprotein Receptor Related Proteins as Regulators of Neural Stem and Progenitor Cell Function

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Loic Auderset ◽  
Lila M. Landowski ◽  
Lisa Foa ◽  
Kaylene M. Young
Keyword(s):  
Progenitor Cells ◽  
Tyrosine Kinases ◽  
Cell Function ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cell Types ◽  
Projection Neurons ◽  
Low Density ◽  
Cell Functions

The central nervous system (CNS) is a highly organised structure. Many signalling systems work in concert to ensure that neural stem cells are appropriately directed to generate progenitor cells, which in turn mature into functional cell types including projection neurons, interneurons, astrocytes, and oligodendrocytes. Herein we explore the role of the low density lipoprotein (LDL) receptor family, in particular family members LRP1 and LRP2, in regulating the behaviour of neural stem and progenitor cells during development and adulthood. The ability of LRP1 and LRP2 to bind a diverse and extensive range of ligands, regulate ligand endocytosis, recruit nonreceptor tyrosine kinases for direct signal transduction and signal in conjunction with other receptors, enables them to modulate many crucial neural cell functions.

scholarly journals Binding of Low Density Lipoprotein to Platelet Apolipoprotein E Receptor 2′ Results in Phosphorylation of p38MAPK

2004 ◽  
Vol 279 (50) ◽  
pp. 52526-52534 ◽  
Author(s):  
Suzanne J. A. Korporaal ◽  
Ingrid A. M. Relou ◽  
Miranda van Eck ◽  
Vera Strasser ◽  
Martineke Bezemer ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Family Member ◽  
Tyrosine Kinases ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Mitogen Activated Protein Kinase ◽  
Low Density ◽  
Platelet Surface ◽  
Receptor Family

Binding of low density lipoprotein (LDL) to platelets enhances platelet responsiveness to various aggregation-inducing agents. However, the identity of the platelet surface receptor for LDL is unknown. We have previously reported that binding of the LDL component apolipoprotein B100 to platelets induces rapid phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Here, we show that LDL-dependent activation of this kinase is inhibited by receptor-associated protein (RAP), an inhibitor of members of the LDL receptor family. Confocal microscopy revealed a high degree of co-localization of LDL and a splice variant of the LDL receptor family member apolipoprotein E receptor-2 (apoER2′) at the platelet surface, suggesting that apoER2′ may contribute to LDL-induced platelet signaling. Indeed, LDL was unable to induce p38MAPKactivation in platelets of apoER2-deficient mice. Furthermore, LDL bound efficiently to soluble apoER2′, and the transient LDL-induced activation of p38MAPKwas mimicked by an anti-apoER2 antibody. Association of LDL to platelets resulted in tyrosine phosphorylation of apoER2′, a process that was inhibited in the presence of PP1, an inhibitor of Src-like tyrosine kinases. Moreover, phosphorylated but not native apoER2′ co-precipitated with the Src family member Fgr. This suggests that exposure of platelets to LDL induces association of apoER2′ to Fgr, a kinase that is able to activate p38MAPK. In conclusion, our data indicate that apoER2′ contributes to LDL-dependent sensitization of platelets.

Identification of Apolipoprotein E Receptor 2′ as the Low-Density Lipoprotein Receptor on Platelets.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1549-1549
Author(s):  
Jan-Willem N. Akkerman ◽  
Suzanne J.A. Korporaal ◽  
Ingrid A.M. Relou ◽  
Miranda Van Eck ◽  
Martineke Bezemer ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Family Member ◽  
Tyrosine Kinases ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Platelet Surface ◽  
Density Lipoprotein Receptor ◽  
Receptor Family

Abstract The interaction of platelets with low-density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis and thrombosis. Previously, we have shown that native LDL (nLDL) is a mild activator of platelets increasing their sensitivity to aggregation-inducing agents. Binding of nLDL to platelets was saturable, reversible and initiated signal transduction to p38MAPK suggesting the involvement of a receptor. A peptide mimic of the B-site in apoB100 resembled nLDL in its platelet-activating properties, suggesting that the receptor is a member of the LDL-receptor family. Platelets from familial hypercholesterolemia patients, who lack or have a defective apoB/E receptor, responded normally to nLDL and an antibody against this receptor left nLDL-induced activation of normal platelets undisturbed, excluding the involvement of the classical LDL (apoB/E)-receptor. In this study, we provide evidence that nLDL initiates platelet signaling to p38MAPK via a splice variant of the LDL-receptor family member Apolipoprotein E Receptor 2 (ApoER2′). This conclusion is based on (i) blockade of nLDL-induced p38MAPK activation by receptor-associated protein (RAP), an inhibitor of ligand binding to members of the LDL-receptor family, (ii) confocal microscopy showing a high degree of co-localization of nLDL and ApoER2′ at the platelet surface, (iii) binding of both nLDL and the B-site peptide to soluble ApoER2′, (iv) activation of p38MAPK by an anti-ApoER2 antibody with similar kinetics as nLDL, and (v) tyrosine phosphorylation of ApoER2′ upon binding of nLDL. The nLDL-induced phosphorylation of ApoER2′ could be abolished by PP1, an inhibitor of Src-like tyrosine kinases. In the absence of PP1, ApoER2′ phosphorylation was accompanied by co-association with the Src-family member Fgr. We conclude that binding of nLDL to platelets involves ApoER2′. Upon nLDL binding, the receptor is phosphorylated which induces the recruitment of Fgr, a kinase known to activate p38MAPK. The ApoER2′-Fgr complex subsequently activates p38MAPK, an upstream element in the formation of thromboxane A2 that primes the platelets to further stimulation by aggregation-inducing agents.

scholarly journals Interaction of 4-hydroxynonenal-modified low-density lipoproteins with the fibroblast apolipoprotein B/E receptor

1986 ◽  
Vol 234 (1) ◽  
pp. 245-248 ◽  
Author(s):  
W Jessup ◽  
G Jurgens ◽  
J Lang ◽  
H Esterbauer ◽  
R T Dean
Keyword(s):  
Apolipoprotein B ◽  
Negative Charge ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipid Peroxidation Product ◽  
Modified Low Density Lipoproteins ◽  
Peroxidation Product

The incorporation of the lipid peroxidation product 4-hydroxynonenal into low-density lipoprotein (LDL) increases the negative charge of the particle, and decreases its affinity for the fibroblast LDL receptor. It is suggested that this modification may occur in vivo, and might promote atherogenesis.

scholarly journals Detection of the low-density-lipoprotein receptor with biotin-low-density lipoprotein. A rapid new method for ligand blotting

1985 ◽  
Vol 229 (3) ◽  
pp. 785-790 ◽  
Author(s):  
D P Wade ◽  
B L Knight ◽  
A K Soutar
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Receptor Protein ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Cell Extracts ◽  
Density Lipoprotein Receptor ◽  
A New Technique

A new technique has been developed to identify low-density-lipoprotein (LDL) receptors on nitrocellulose membranes, after transfer from SDS/polyacrylamide gels, by ligand blotting with biotin-modified LDL. Modification with biotin hydrazide of periodate-oxidized lipoprotein sugar residues does not affect the ability of the lipoprotein to bind to the LDL receptor. Bound lipoprotein is detected with high sensitivity by a streptavidin-biotin-peroxidase complex, and thus this method eliminates the need for specific antibodies directed against the ligand. The density of the bands obtained is proportional to the amount of pure LDL receptor protein applied to the SDS/polyacrylamide gel, so that it is possible to quantify LDL receptor protein in cell extracts. Biotin can be attached to other lipoproteins, for example very-low-density lipoproteins with beta-mobility, and thus the method will be useful in the identification and isolation of other lipoprotein receptors.

scholarly journals Ligand selectivity of 105 kDa and 130 kDa lipoprotein-binding proteins in vascular-smooth-muscle-cell membranes is unique

1996 ◽  
Vol 317 (1) ◽  
pp. 297-304 ◽  
Author(s):  
Valery N. BOCHKOV ◽  
Vsevolod A. TKACHUK ◽  
Maria P. PHILIPPOVA ◽  
Dimitri V. STAMBOLSKY ◽  
Fritz R. BÜHLER ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Binding Proteins ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Dextran Sulphate ◽  
Apo B ◽  
Ligand Selectivity ◽  
Lipoprotein Binding

Using ligand blotting techniques, with low-density lipoprotein (LDL) as ligand, we have previously described the existence of atypical lipoprotein-binding proteins (105 kDa and 130 kDa) in membranes from human aortic medial tissue. The present study demonstrates that these proteins are also present in membranes from cultured human (aortic and mesenteric) and rat (aortic) vascular smooth-muscle cells (VSMCs). To assess the relationship of 105 and 130 kDa lipoprotein-binding proteins to known lipoprotein receptors, ligand binding specificity was studied. We tested effects of substances known to antagonize ligand binding to either the LDL [apolipoprotein B,E (apo B,E)] receptor (dextran sulphate, heparin, pentosan polysulphate, protamine, spermine, histone), the scavenger receptor (dextran sulphate, fucoidin), the very-low-density-lipoprotein (VLDL) receptor [receptor-associated protein (RAP)], or LDL receptor-related protein (RAP, α2-macroglobulin, lipoprotein lipase, exotoxin-A). None of these substances, with the exception of dextran sulphate, influenced binding of LDL to either 105 or 130 kDa proteins. Sodium oleate or oleic acid, known stimuli for the lipoprotein binding activity of the lipolysis-stimulated receptor, were also without effect. LDL binding to 105 and 130 kDa proteins was inhibited by anti-LDL (apo B) antibodies. LDL and VLDL bound to 105 and 130 kDa proteins with similar affinities (蝶50 μg/ml). The unique ligand selectivity of 105 and 130 kDa proteins supports the existence of a novel lipoprotein-binding protein that is distinct from all other currently identified LDL receptor family members. The similar ligand selectivity of 105 and 130 kDa proteins suggests that they may represent variant forms of an atypical lipoprotein-binding protein.

Characterization of a family of gamma-ray-induced CHO mutants demonstrates that the ldlA locus is diploid and encodes the low-density lipoprotein receptor

1986 ◽  
Vol 6 (9) ◽  
pp. 3268-3277
Author(s):  
R D Sege ◽  
K F Kozarsky ◽  
M Krieger
Keyword(s):  
Gamma Irradiation ◽  
Cho Cells ◽  
Gamma Ray ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Chinese Hamster ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Ldl Receptors

The ldlA locus is one of four Chinese hamster ovary (CHO) cell loci which are known to be required for the synthesis of functional low-density lipoprotein (LDL) receptors. Previous studies have suggested that the ldlA locus is diploid and encodes the LDL receptor. To confirm this assignment, we have isolated a partial genomic clone of the Chinese hamster LDL receptor gene and used this and other nucleic acid and antibody probes to study a family of ldlA mutants isolated after gamma-irradiation. Our analysis suggests that there are two LDL receptor alleles in wild-type CHO cells. Each of the three mutants isolated after gamma-irradiation had detectable deletions affecting one of the two LDL receptor alleles. One of the mutants also had a disruption of the remaining allele, resulting in the synthesis of an abnormal receptor precursor which was not subject to Golgi-associated posttranslational glycoprotein processing. The correlation of changes in the expression, structure, and function of LDL receptors with deletions in the LDL receptor genes in these mutants directly demonstrated that the ldlA locus in CHO cells is diploid and encodes the LDL receptor. In addition, our analysis suggests that CHO cells in culture may contain a partial LDL receptor pseudogene.

Isolation and characterization of an extragenic suppressor of the low-density lipoprotein receptor-deficient phenotype of a Chinese hamster ovary cell mutant

1989 ◽  
Vol 9 (11) ◽  
pp. 4799-4806
Author(s):  
P Reddy ◽  
M Krieger
Keyword(s):  
Structural Gene ◽  
Chinese Hamster Ovary ◽  
Low Density Lipoprotein ◽  
Chinese Hamster ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Ovary Cell ◽  
Low Density ◽  
Extragenic Suppressor ◽  
Extragenic Suppression

ldlC cells are low-density lipoprotein (LDL) receptor-deficient Chinese hamster ovary cell mutants which express pleiotropic defects in Golgi-associated glycosylation reactions. The dramatically reduced stability of the abnormally glycosylated LDL receptors in ldlC cells was shown to be due, in part, to rapid proteolysis and release of a large extracellular fragment of the receptor into the medium. A set of spontaneously arising LDL receptor-positive revertants of ldlC cells has been isolated. One of these, RevC-13, exhibits the glycosylation defects characteristic of the original ldlC mutant, suggesting that restoration of receptor activity was due to extragenic suppression. This suppression was due to a dramatic increase in the rate of LDL receptor synthesis rather than to an increase in the stability of the abnormally glycosylated receptors. Increased receptor synthesis was not due to receptor gene amplification. The increased LDL receptor activity was subject to normal sterol regulation. Analysis of the RevC-13 extragenic suppressor activity in a series of hybrid cells showed that RevC-13 suppression was a codominant trait that acted in cis to the LDL receptor structural gene (ldlA). Thus, the extragenic suppression in RevC-13 cells has defined a genetic element which is either part of or linked to the LDL receptor structural gene and which can control LDL receptor expression.

Sign in / Sign up

Export Citation Format

Share Document