LDL Receptor–Related Protein-1

Gonias, Steven L.; Campana, W. Marie

doi:10.1016/j.ajpath.2013.08.029

Cited by 149 publications

(112 citation statements)

References 99 publications

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“…We studied EI-tPA, as opposed to active tPA, to avoid off-target effects related to the protease activity of this protein. ERK1/2 activation in response to EI-tPA was blocked by the LRP1 antagonist RAP, suggesting an essential role for LRP1 (Gonias and Campana, 2014; Herz and Strickland, 2001). ERK1/2 activation also was blocked by treating the cells with 1 mM MβCD for 30 min.…”

Section: Resultsmentioning

confidence: 97%

“…We initiated the current study to understand why LRP1 may function as a cell-signaling receptor selectively in specific cell-types (Gonias and Campana, 2014). Our previous studies suggested that the fractional distribution of LRP1 into lipid rafts may be cell type-specific (Wu and Gonias, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…LDL Receptor-related Protein-1 (LRP1) is a type 1 transmembrane protein and member of the LDL Receptor (LDL-R) gene family, implicated in endocytosis, phagocytosis, efferocytosis, and cell-signaling (Gonias and Campana, 2014; Herz and Strickland, 2001). LRP1 ligands are numerous and structurally diverse.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, the activity of LRP1 in cell-signaling also appears to be cell type-specific (Gonias and Campana, 2014). In neurons, LRP1-activated cell-signaling has been implicated in neuronal survival (Fuentealba et al, 2009; Hayashi et al, 2007), neurite outgrowth (Mantuano et al, 2008; Matsuo et al, 2011; Qiu et al, 2004; Shi et al, 2009), growth cone navigation (Landowski et al, 2016), synaptic transmission (May et al, 2004), and long-term potentiation (Zhuo et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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The activities of LDL Receptor-related Protein-1 (LRP1) compartmentalize into distinct plasma membrane microdomains

Laudati

Gilder

Lam

et al. 2016

Molecular and Cellular Neuroscience

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LDL Receptor-related Protein-1 (LRP1) is an endocytic receptor for diverse ligands. In neurons and neuron-like cells, ligand-binding to LRP1 initiates cell-signaling. Herein, we show that in PC12 and N2a neuron-like cells, LRP1 distributes into lipid rafts and non-raft plasma membrane fractions. When lipid rafts were disrupted, using methyl-β-cyclodextrin or fumonisin B1, activation of Src family kinases and ERK1/2 by the LRP1 ligands, tissue-type plasminogen activator and activated α2-macroglobulin, was blocked. Biological consequences of activated LRP1 signaling, including neurite outgrowth and cell growth, also were blocked. The effects of lipid raft disruption on ERK1/2 activation and neurite outgrowth, in response to LRP1 ligands, were reproduced in experiments with cerebellar granule neurons in primary culture. Because the reagents used to disrupt lipid rafts may have effects on the composition of the plasma membrane outside lipid rafts, we studied the effects of these reagents on LRP1 activities unrelated to cell-signaling. Lipid raft disruption did not affect the total ligand binding capacity of LRP1, the affinity of LRP1 for its ligands, or its endocytic activity. These results demonstrate that well described activities of LRP1 require localization of this receptor to distinct plasma membrane microdomains.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The activities of LDL Receptor-related Protein-1 (LRP1) compartmentalize into distinct plasma membrane microdomains

Laudati

Gilder

Lam

et al. 2016

Molecular and Cellular Neuroscience

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“…We went further to uncover the underlying mechanism. LRP1 interacts with over 60 ligands (Gonias and Campana 2014; Lillis et al 2008; Ling et al 2004; Spijkers et al 2008; Spuch et al 2012; Vaillant et al 2007) and depending on the ligand the downstream effect of binding can be drastically different. ApoE, abundantly expressed in the CNS (Xu et al 2006), is one of the major LRP1 ligands.…”

Section: Discussionmentioning

confidence: 99%

Low‐density lipoprotein receptor‐related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation

Safina

Schlitt

Romeo

et al. 2016

Glia

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The LDL family of receptors and its member LRP1 have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation. In the current study we show that LeX-glycosylated LRP1 is also expressed in the stem cell compartment of the developing spinal cord and has broader functions in the developing CNS. We have investigated the basic properties of LRP1 conditional knockout on the neural stem/progenitor cells (NSPCs) from the cortex and the spinal cord, created by means of Cre-loxp mediated recombination in vitro. The functional status of LRP1-deficient cells has been studied using proliferation, differentiation and apoptosis assays. LRP1 deficient NSPCs from both CNS regions demonstrated altered differentiation profiles. Their differentiation capacity towards oligodendrocyte progenitor cells (OPCs), mature oligodendrocytes and neurons was reduced. In contrast, astrocyte differentiation was promoted. Moreover, LRP1 deletion had a negative effect on NSPCs proliferation and survival. Our observations suggest that LRP1 facilitates NSPCs differentiation via interaction with ApoE. Upon ApoE4 stimulation wild type NSPCs generated more oligodendrocytes, but LRP1 knockout cells showed no response. The effect of ApoE seems to be independent of cholesterol uptake, but is rather mediated by downstream MAPK and Akt activation.

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Multi‐omics data identified TP53 and LRP1B as key regulatory gene related to immune phenotypes via EPCAM in HCC

et al. 2022

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Background Many studies showed that the prognosis of hepatocellular carcinoma (HCC) was significantly associated with the expressions of TP53 and LRP1B. However, the potential influence of the two genes on the malignant progression of HCC is still to be expounded. Methods According to the correlation analysis between immune cells and expression levels of TP53 and LRP1B, we filtered the immune cells to perform unsupervised clustering analysis. Integration of multi‐omic data analysis identified genetic alteration and epigenetic alteration. In addition, pathway analysis was used to explore the potential function of the differentially expressed mRNAs. According to the differentially expressed genes, we established an interaction network to seek the hub gene. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a prognosis model. Results The unsupervised clustering analysis showed that the cluster A1 showed the highest immune cell levels and the cluster B2 showed the lowest immune cell levels. Multi‐omics data analysis identified that somatic mutations, copy number variations, and DNA methylation levels had significant differences between cluster A1 and cluster B2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the upregulated mRNAs in the cluster A1 were mainly concentrated in T cell activation, external side of plasma membrane, receptor ligand activity, and cytokine−cytokine receptor interaction. Importantly, the EPCAM was identified as a critical node in the lncRNAs–miRNAs–mRNAs regulatory network correlated with the immune phenotypes. In addition, based on differentially expressed genes between cluster A1 and cluster B2, the prognostic model established by LASSO could predict the overall survival (OS) of HCC accurately. Conclusions The results indicated that the TP53 and LRP1B acted as the key genes in regulating the immune phenotypes of HCC via EPCAM.

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LDL Receptor–Related Protein-1

Cited by 149 publications

References 99 publications

The activities of LDL Receptor-related Protein-1 (LRP1) compartmentalize into distinct plasma membrane microdomains

The activities of LDL Receptor-related Protein-1 (LRP1) compartmentalize into distinct plasma membrane microdomains

Low‐density lipoprotein receptor‐related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation

Multi‐omics data identified TP53 and LRP1B as key regulatory gene related to immune phenotypes via EPCAM in HCC

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