A Hyaluronan Receptor for Endocytosis (HARE) Link Domain N-Glycan Is Required for Extracellular Signal-regulated Kinase (ERK) and Nuclear Factor-κB (NF-κB) Signaling in Response to the Uptake of Hyaluronan but Not Heparin, Dermatan Sulfate, or Acetylated Low Density Lipoprotein (LDL)

Pandey, Madhu; Weigel, Paul H.

doi:10.1074/jbc.m114.565846

Cited by 19 publications

(16 citation statements)

References 41 publications

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“…However, it is more likely that stabilin-2 expressed on the splenic sinusoidal endothelium acts as a key mediator in the directed shuttling of FVIII antigen in a VWF-dependent manner through marginal zone macrophage and marginal B cell compartments of the spleen (11,59,60). Furthermore, engagement of stabilin-2 initiates signaling through extracellular signal-regulated kinases 1 and 2 (ERK1/2), and can induce NF-κB activation of proinflammatory gene expression that can, in turn, enhance the likelihood of an immune response (61). As evidence for this hypothesis, the …”

Section: Discussionmentioning

confidence: 99%

The endothelial cell receptor stabilin-2 regulates VWF-FVIII complex half-life and immunogenicity

Swystun¹,

Lai²,

Notley³

et al. 2018

Journal of Clinical Investigation

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variants demonstrated that the STAB2 p.E2377K variant associates with a 33.6% and 26.8% increase in VWF and FVIII levels, respectively (25), suggesting that stabilin-2 is a significant regulator of plasma VWF-FVIII levels. Based on its known function and association with plasma VWF levels, stabilin-2 may act as a clearance receptor for VWF and/or FVIII; however, the mechanistic basis for this relationship has not been assessed.In addition to facilitating protein clearance, binding of VWF-FVIII to endocytic receptors can regulate interactions with cells in the immune system. The development of FVIII neutralizing antibodies (termed inhibitors) in response to infused FVIII replace-STAB2 encodes stabilin-2, a class H scavenger receptor expressed on the sinusoidal endothelial cells of the liver, spleen, and lymphatics that functions as a clearance receptor for hyaluronic acid and other glycosaminoglycans (21-23). Stabilin-2 is composed of repetitive extracellular fasciclin and EGF-like domains with a single X-link domain that is C-type lectin-like, located near its transmembrane region. Subsequent to the CHARGE study, additional GWAS-based publications have independently confirmed that common STAB2 variants associate with plasma

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Section: Discussionmentioning

confidence: 99%

The endothelial cell receptor stabilin-2 regulates VWF-FVIII complex half-life and immunogenicity

Swystun¹,

Lai²,

Notley³

et al. 2018

Journal of Clinical Investigation

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“…FAK/SRC-mediated ERK activation is involved in signaling event for stem cell development. Additional receptor proteins for HA include intracellular adhesion molecule-1 (ICAM-1) (Bruynzeel et al, 1993), hyaluronan receptor for endocytosis (HARE) (Pandey and Weigel, 2014), and lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 (Banerji et al, 1999; Lawrance et al, 2016). Clustering of LYVE-1 is essential for HA binding in the lymphatic endothelial cells (Lawrance et al, 2016).…”

Section: Ha Receptors and Signalingmentioning

confidence: 99%

HYAL-2–WWOX–SMAD4 Signaling in Cell Death and Anticancer Response

Hsu

Chiang

Sze

et al. 2016

Front. Cell Dev. Biol.

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Hyaluronidase HYAL-2 is a membrane-anchored protein and also localizes, in part, in the lysosome. Recent study from animal models revealed that both HYAL-1 and HYAL-2 are essential for the metabolism of hyaluronan (HA). Hyal-2 deficiency is associated with chronic thrombotic microangiopathy with hemolytic anemia in mice due to over accumulation of high molecular size HA. HYAL-2 is essential for platelet generation. Membrane HYAL-2 degrades HA bound by co-receptor CD44. Also, in a non-canonical signal pathway, HYAL-2 serves as a receptor for transforming growth factor beta (TGF-β) to signal with downstream tumor suppressors WWOX and SMAD4 to control gene transcription. When SMAD4 responsive element is overly driven by the HYAL-2–WWOX–SMAD4 signaling complex, cell death occurs. When rats are subjected to traumatic brain injury, over accumulation of a HYAL-2–WWOX complex occurs in the nucleus to cause neuronal death. HA induces the signaling of HYAL-2–WWOX–SMAD4 and relocation of the signaling complex to the nucleus. If the signaling complex is overexpressed, bubbling cell death occurs in WWOX-expressing cells. In addition, a small synthetic peptide Zfra (zinc finger-like protein that regulates apoptosis) binds membrane HYAL-2 of non-T/non-B spleen HYAL-2+ CD3− CD19− Z lymphocytes and activates the cells to generate memory anticancer response against many types of cancer cells in vivo. Whether the HYAL-2–WWOX–SMAD4 signaling complex is involved is discussed. In this review and opinion article, we have updated the current knowledge of HA, HYAL-2 and WWOX, HYAL-2–WWOX–SMAD4 signaling, bubbling cell death, and Z cell activation for memory anticancer response.

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“…Lysoplex application to a relatively small set of patients resulted in the identification of several homozygous or compound heterozygous mutations in putative novel disease genes for NCLs. These are: STAB2, that encodes a cell receptor that enables the scavenging and clearance of multiple ligands from the circulation salvaging their building block monomers by lysosomal degradation, as well as MAPK1/ERK2-MAPK3/ERK1 activated signaling, 64,65 AGAP1 that encodes an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPaseactivating protein, 66 and PLCG2 that encodes a transmembrane signaling enzyme whose gain-of-function mutations have been associated with autoimmune and inflammatory diseases mediated by B cells. 67 More data, such as the identification of additional families and/or functional assays, are needed to definitely prove the involvement of the above candidate genes in NCL pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Lysoplex: An efficient toolkit to detect DNA sequence variations in the autophagy-lysosomal pathway

et al. 2015

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The autophagy-lysosomal pathway (ALP) regulates cell homeostasis and plays a crucial role in human diseases, such as lysosomal storage disorders (LSDs) and common neurodegenerative diseases. Therefore, the identification of DNA sequence variations in genes involved in this pathway and their association with human diseases would have a significant impact on health. To this aim, we developed Lysoplex, a targeted next-generation sequencing (NGS) approach, which allowed us to obtain a uniform and accurate coding sequence coverage of a comprehensive set of 891 genes involved in lysosomal, endocytic, and autophagic pathways. Lysoplex was successfully validated on 14 different types of LSDs and then used to analyze 48 mutation-unknown patients with a clinical phenotype of neuronal ceroid lipofuscinosis (NCL), a genetically heterogeneous subtype of LSD. Lysoplex allowed us to identify pathogenic mutations in 67% of patients, most of whom had been unsuccessfully analyzed by several sequencing approaches. In addition, in 3 patients, we found potential disease-causing variants in novel NCL candidate genes. We then compared the variant detection power of Lysoplex with data derived from public whole exome sequencing (WES) efforts. On average, a 50% higher number of validated amino acid changes and truncating variations per gene were identified. Overall, we identified 61 truncating sequence variations and 488 missense variations with a high probability to cause loss of function in a total of 316 genes. Interestingly, some loss-of-function variations of genes involved in the ALP pathway were found in homozygosity in the normal population, suggesting that their role is not essential. Thus, Lysoplex provided a comprehensive catalog of sequence variants in ALP genes and allows the assessment of their relevance in cell biology as well as their contribution to human disease.

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A Hyaluronan Receptor for Endocytosis (HARE) Link Domain N-Glycan Is Required for Extracellular Signal-regulated Kinase (ERK) and Nuclear Factor-κB (NF-κB) Signaling in Response to the Uptake of Hyaluronan but Not Heparin, Dermatan Sulfate, or Acetylated Low Density Lipoprotein (LDL)

Cited by 19 publications

References 41 publications

The endothelial cell receptor stabilin-2 regulates VWF-FVIII complex half-life and immunogenicity

The endothelial cell receptor stabilin-2 regulates VWF-FVIII complex half-life and immunogenicity

HYAL-2–WWOX–SMAD4 Signaling in Cell Death and Anticancer Response

Lysoplex: An efficient toolkit to detect DNA sequence variations in the autophagy-lysosomal pathway

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