The 39-kDa Receptor-associated Protein Modulates Lipoprotein Catabolism by Binding to LDL Receptors

Medh, Jheem D.; Fry, Glenna L.; Bowen, Susan L.; Pladet, M W; Strickland, Dudley K.; Chappell, David

doi:10.1074/jbc.270.2.536

Cited by 113 publications

(94 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RAP is an intracellular chaperone that binds tightly to the LRP1 α-chain, with the pitfall that other members of the LDL receptor family are also detected (38,39). In uninjured rat sciatic nerve, a single band with an apparent mass equivalent to that of the LRP1 α-chain was observed ( Figure 1C).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A shed form of LDL receptor–related protein–1 regulates peripheral nerve injury and neuropathic pain in rodents

Gaultier

Arandjelovic

et al. 2008

J. Clin. Invest.

View full text Add to dashboard Cite

Injury to the peripheral nervous system (PNS) initiates a response controlled by multiple extracellular mediators, many of which contribute to the development of neuropathic pain. Schwann cells in an injured nerve demonstrate increased expression of LDL receptor-related protein-1 (LRP1), an endocytic receptor for diverse ligands and a cell survival factor. Here we report that a fragment of LRP1, in which a soluble or shed form of LRP1 with an intact α-chain (sLRP-α), was shed by Schwann cells in vitro and in the PNS after injury. Injection of purified sLRP-α into mouse sciatic nerves prior to chronic constriction injury (CCI) inhibited p38 MAPK activation (P-p38) and decreased expression of TNF-α and IL-1β locally. sLRP-α also inhibited CCI-induced spontaneous neuropathic pain and decreased inflammatory cytokine expression in the spinal dorsal horn, where neuropathic pain processing occurs. In cultures of Schwann cells, astrocytes, and microglia, sLRP-α inhibited TNF-α-induced activation of p38 MAPK and ERK/MAPK. The activity of sLRP-α did not involve TNF-α binding, but rather glial cell preconditioning, so that the subsequent response to TNF-α was inhibited. Our results show that sLRP-α is biologically active and may attenuate neuropathic pain. In the PNS, the function of LRP1 may reflect the integrated activities of the membrane-anchored and shed forms of LRP1.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Most LRP1 ligands bind to clusters of complement-like repeats in the α-chain, which may be fully blocked by GST-RAP (1,11,38,39). Two protocols were executed to test whether GST-RAP inhibits the activity of sLRP-α in vivo in the injured nerve.…”

Section: Figurementioning

confidence: 99%

A shed form of LDL receptor–related protein–1 regulates peripheral nerve injury and neuropathic pain in rodents

Gaultier

Arandjelovic

et al. 2008

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The receptors have high affinity for their ligands and broad specificity. They recognize not only lipoproteins but also a variety of nonlipoprotein ligands, including urokinase and tissue plasminogen activator with their inhibitors and participate in different physiological processes (26,(37)(38)(39)(40)(41)(42)(43)(44)(45). Ten members of this family are known to date: the LDL receptor itself, ␣ 2 -macroglobulin receptor/low density lipoprotein receptor-related protein (␣ 2 MR/LRP), very low density lipoprotein receptor, Heymann nephritis antigen/ megalin/gp330, chicken vitellogenin receptor, Drosophila Yolkless, chicken LR8B, placental calcium sensor protein (29), the newly discovered apolipoprotein E receptor 2 (apoER2) (30), and LR11 (31).…”

Section: Discussionmentioning

confidence: 99%

Collagenase-3 Binds to a Specific Receptor and Requires the Low Density Lipoprotein Receptor-related Protein for Internalization

Barmina

Walling

Fiacco

et al. 1999

Journal of Biological Chemistry

111

View full text Add to dashboard Cite

We have previously identified a specific receptor for collagenase-3 that mediates the binding, internalization, and degradation of this ligand in UMR 106-01 rat osteoblastic osteosarcoma cells. In the present study, we show that collagenase-3 binding is calcium-dependent and occurs in a variety of cell types, including osteoblastic and fibroblastic cells. We also present evidence supporting a two-step mechanism of collagenase-3 binding and internalization involving both a specific collagenase-3 receptor and the low density lipoprotein receptorrelated protein. Ligand blot analysis shows that 125 Icollagenase-3 binds specifically to two proteins (ϳ170 kDa and ϳ600 kDa) present in UMR 106-01 cells. Western blotting identified the 600-kDa protein as the low density lipoprotein receptor-related protein. Our data suggest that the 170-kDa protein is a specific collagenase-3 receptor. Low density lipoprotein receptor-related protein-null mouse embryo fibroblasts bind but fail to internalize collagenase-3, whereas UMR 106-01 and wildtype mouse embryo fibroblasts bind and internalize collagenase-3. Internalization, but not binding, is inhibited by the 39-kDa receptor-associated protein. We conclude that the internalization of collagenase-3 requires the participation of the low density lipoprotein receptor-related protein and propose a model in which the cell surface interaction of this ligand requires a sequential contribution from two receptors, with the collagenase-3 receptor acting as a high affinity primary binding site and the low density lipoprotein receptor-related protein mediating internalization. Collagenase-3 (MMP-13)1 is a member of the matrix metalloproteinase family of enzymes, which participates in extracellular matrix remodeling (1). Members of this family have a number of structural and functional features in common. In addition to sharing a similar domain structure, all are synthesized in inactive form, function at neutral pH, and require intrinsic zinc and calcium ions for their activity. Collagenase-3 is a highly regulated enzyme that cleaves native fibrillar collagens of types I, II, and III. The 57-kDa proenzyme is converted to its active 52-kDa form by the plasmin activation cascade, as well as by cathepsin B, stromelysin, and plasma kallikrein (2, 3). Collagenase-3 activity is inhibited by a family of tissue inhibitors of metalloproteinases (4, 5). A range of hormones and agents can also regulate expression of collagenase-3 (6). Parathyroid hormone is one of the hormones participating in this process. Osteoblastic cells respond to parathyroid hormone by increasing collagenase-3 synthesis (6 -8), plasminogen activator activity (9), and tissue inhibitors of metalloproteinases expression (8). In addition, experiments with UMR 106-01 rat osteosarcoma cells showed that over 80% of exogenous rat collagenase-3 was removed from the medium after 8 h of incubation (10). This rapid removal of rat collagenase-3 from the medium suggested the existence of a specific receptor that represents another level of regu...

show abstract

“…As shown in Fig. 6A, neither the inhibitory antibodies against CRT or LRP1 (46) nor LRP1 receptorassociated protein (RAP), which inhibits CRT-LRP1 binding (43,47,48), showed inhibition on LPS/cytokine-activated PEM phagocytosis toward RBCs and splenocytes. However, these same reagents significantly inhibited phagocytosis toward apoptotic cells (Fig.…”

Section: What Is the Phagocytic Receptor On Macrophages For Uptakingmentioning

confidence: 92%

Cd47-Sirpα interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells

Bian

Shi

Guo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

121

View full text Add to dashboard Cite

Rapid clearance of adoptively transferred Cd47-null (Cd47−/−) cells in congeneic WT mice suggests a critical self-recognition mechanism, in which CD47 is the ubiquitous marker of self, and its interaction with macrophage signal regulatory protein α (SIRPα) triggers inhibitory signaling through SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and tyrosine phosphatase SHP-1/2. However, instead of displaying self-destruction phenotypes, Cd47−/− mice manifest no, or only mild, macrophage phagocytosis toward self-cells except under the nonobese diabetic background. Studying our recently established Sirpα-KO (Sirpα−/−) mice, as well as Cd47−/− mice, we reveal additional activation and inhibitory mechanisms besides the CD47-SIRPα axis dominantly controlling macrophage behavior. Sirpα−/− mice and Cd47−/− mice, although being normally healthy, develop severe anemia and splenomegaly under chronic colitis, peritonitis, cytokine treatments, and CFA-/LPS-induced inflammation, owing to splenic macrophages phagocytizing self-red blood cells. Ex vivo phagocytosis assays confirmed general inactivity of macrophages from Sirpα−/− or Cd47−/− mice toward healthy self-cells, whereas they aggressively attack toward bacteria, zymosan, apoptotic, and immune complex-bound cells; however, treating these macrophages with IL-17, LPS, IL-6, IL-1β, and TNFα, but not IFNγ, dramatically initiates potent phagocytosis toward self-cells, for which only the Cd47-Sirpα interaction restrains. Even for macrophages from WT mice, phagocytosis toward Cd47−/− cells does not occur without phagocytic activation. Mechanistic studies suggest a PKC-Syk–mediated signaling pathway, to which IL-10 conversely inhibits, is required for activating macrophage self-targeting, followed by phagocytosis independent of calreticulin. Moreover, we identified spleen red pulp to be one specific tissue that provides stimuli constantly activating macrophage phagocytosis albeit lacking in Cd47−/− or Sirpα−/− mice.

show abstract

The 39-kDa Receptor-associated Protein Modulates Lipoprotein Catabolism by Binding to LDL Receptors

Cited by 113 publications

References 46 publications

A shed form of LDL receptor–related protein–1 regulates peripheral nerve injury and neuropathic pain in rodents

A shed form of LDL receptor–related protein–1 regulates peripheral nerve injury and neuropathic pain in rodents

Collagenase-3 Binds to a Specific Receptor and Requires the Low Density Lipoprotein Receptor-related Protein for Internalization

Cd47-Sirpα interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells

Contact Info

Product

Resources

About