The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Martínez, Vanesa G.; Moestrup, Søren K.; Holmskov, Uffe; Mollenhauer, Jan; Lozano, Francisco

doi:10.1124/pr.111.004523

Cited by 160 publications

(160 citation statements)

References 418 publications

(377 reference statements)

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“…32 These receptors are known to bind and internalize self-and non-self-molecules and participate in cellular functions such as antigen presentation, inflammation, and clearance. 32,33 We evaluated the possible role of SRs in ADAMTS13 uptake by pretreating macrophages with polyanionic compounds such as dextran sulfate and heparin. ADAMTS13 uptake was significantly reduced by both compounds (supplemental Figure 1D-E).…”

Section: Polyanionic Ligands Block the Internalization Of Adamts13 Bymentioning

confidence: 99%

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

et al. 2017

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Key Points• Uptake of ADAMTS13 by macrophages is not dependent on the macrophage mannose receptor.• CD163 promotes internalization of ADAMTS13 by macrophages.Internalization of ADAMTS13 by macrophages may contribute to its clearance from the circulation. Here we investigated endocytic mechanisms that contribute to the uptake of ADAMTS13 by macrophages. Human monocyte-derived macrophages were used to monitor the uptake of fluorescently labeled recombinant ADAMTS13 by flow cytometry.Internalization of ADAMTS13 was blocked upon addition of the cell-permeable dynamin inhibitor dynasore. Partial blocking of ADAMTS13 uptake was observed by using mannan;however, uptake was not affected by an antibody that blocked binding to the macrophage mannose receptor CD206, which suggests that other endocytic receptors contribute to the internalization of ADAMTS13 by macrophages. A pull-down with ADAMTS13 and subsequent mass spectrometric analysis identified the class I scavenger receptor CD163 as a candidate receptor for ADAMTS13. Blocking experiments with monoclonal anti-CD163 antibody EDHu-1 resulted in decreased ADAMTS13 internalization by macrophages. Pronounced inhibition of ADAMTS13 uptake by EDHu-1 was observed in CD163 high-expressing macrophages. In agreement with these findings, CD163-expressing Chinese hamster ovary cells were capable of rapidly internalizing ADAMTS13. Surface plasmon resonance revealed binding of ADAMTS13 to scavenger receptor cysteine-rich domains 1-9 and 1-5 of CD163. Taken together, our data identify CD163 as a major endocytic receptor for ADAMTS13 on macrophages.

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Section: Polyanionic Ligands Block the Internalization Of Adamts13 Bymentioning

confidence: 99%

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

et al. 2017

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“…3). To the best of our knowledge, SRCR repeats are not found in other GPCRs, whereas SRCR repeats are often found in proteins associated with immune system functions (Martínez et al, 2011;Sarrias et al, 2004). In contrast to the sponges and other pre-bilaterians, M. leidyi adhesion GPCRs are relatively limited in the number of N-terminal domains and the majority of receptors contain only the 7TM domain and the GPS site.…”

Section: N-terminal Domains Of Pre-bilaterian Adhesionsmentioning

confidence: 98%

The role of G protein-coupled receptors in the early evolution of neurotransmission and the nervous system

Krishnan

Schiöth

2015

Journal of Experimental Biology

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The origin and evolution of the nervous system is one of the most intriguing and enigmatic events in biology. The recent sequencing of complete genomes from early metazoan organisms provides a new platform to study the origins of neuronal gene families. This review explores the early metazoan expansion of the largest integral transmembrane protein family, the G protein-coupled receptors (GPCRs), which serve as molecular targets for a large subset of neurotransmitters and neuropeptides in higher animals. GPCR repertories from four pre-bilaterian metazoan genomes were compared. This includes the cnidarian Nematostella vectensis and the ctenophore Mnemiopsis leidyi, which have primitive nervous systems (nerve nets), the demosponge Amphimedon queenslandica and the placozoan Trichoplax adhaerens, which lack nerve and muscle cells. Comparative genomics demonstrate that the rhodopsin and glutamate receptor families, known to be involved in neurotransmission in higher animals are also widely found in prebilaterian metazoans and possess substantial expansions of rhodopsin-family-like GPCRs. Furthermore, the emerging knowledge on the functions of adhesion GPCRs in the vertebrate nervous system provides a platform to examine possible analogous roles of their closest homologues in pre-bilaterians. Intriguingly, the presence of molecular components required for GPCR-mediated neurotransmission in pre-bilaterians reveals that they exist in both primitive nervous systems and nerve-cell-free environments, providing essential comparative models to better understand the origins of the nervous system and neurotransmission. KEY WORDS: Neuron, GPCR, Nerve net, Synapse, EvolutionIntroduction G protein-coupled receptors (GPCRs) constitute the largest superfamily among membrane bound proteins that control key physiological functions, such as, neurotransmission, hormone releases, and immune responses among others (Katritch et al., 2013; Lagerström and Schiöth, 2008;Rosenbaum et al., 2009). As such, the large range of integral transmembrane proteins in this family respond to subsequent, diverse array of ligands: including neurotransmitters, hormones, lipids, and odorants (Civelli et al., 2013;Shoichet and Kobilka, 2012). GPCRs in mammals are classified into the five main families according to the GRAFS classification: glutamate, rhodopsin, adhesion, frizzled and secretin (Fredriksson et al., 2003). These five GPCR families are associated with various physiological functions, but the roles of the glutamate and the rhodopsin families are particularly well documented for REVIEW Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593,751 24, Uppsala, Sweden.*Authors for correspondence (arunkumar.krishnan@neuro.uu.se; helgi.schioth@neuro.uu.se) neurotransmission and regulation of the nervous system (Niswender and Conn, 2010;Schoepp, 2001). Some functions include synaptic transmission, synapse formation, axon guidance and development of neuronal circuits (Collingridge et al., 2004;Hnasko and Edwards, 2012)...

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“…CD5 is a lymphoid member of the Scavenger receptor cysteine-rich superfamily (SRCR-SF), a group of SRs (Class I, according to the new standardized nomenclature) [19] characterized by the presence of several repeats of a cysteine-rich, 90-110 amino acid-long globular domain with a high degree of structural and phylogenetic conservation [20,21]. CD5 is a type I membrane glycoprotein of 67 kDa exclusively composed of three extracellular SRCR domains in tandem, and a cytoplasmic tail well adapted for signal transduction.…”

Section: Cd5mentioning

confidence: 99%

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

et al. 2017

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Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady-state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis. Therefore, SRs built up sophisticated sensor mechanisms controlling the immune system, which may be exploited to develop novel drugs for cancer immunotherapy. In this review, we focus on the regulation of the anti-tumor immune response by two paradigmatic SRs: the lymphocyte receptor CD5 and the more broadly distributed scavenger receptor class B type 1 (SR-B1). Cancer immunity can be boosted by blockade of SRs working as immune checkpoint inhibitors (CD5) and/or by proper engagement of SRs working as innate danger receptor (SR-B1). Thus, these receptors illustrate both the complexity of targeting SRs in cancer immunotherapy and also the opportunities offered by such an approach. Keywords:Cancer immunotherapy r CD5 r Danger signal r Immune-checkpoint r Scavenger receptor r Scavenger receptor class B type 1 r Toll-like receptors IntroductionThe cancer-immunity cycle can be subverted by tumors at many steps, thus novel therapeutic interventions should be considered for all these possibilities [1]. This cycle starts with the release of tumor antigens and their subsequent capture by professional antigen-presenting cells (mainly, dendritic cells; DCs) for the activation of effector cells of the innate and adaptive immune Correspondence: Dr. Pedro Berraondo e-mail: pberraondol@unav.es system. This is a highly regulated process aimed at maintaining the integrity of the host without inducing significant side effects (e.g., inflammation or autoimmunity) [2]. Tissue homeostasis involves phagocytic processes to remove the excess of native or modified molecules from unviable or stressed cells, as well as from invading microbial agents [3]. Such molecules include lipids, whose intracellular levels should be carefully controlled to sustain proper cell metabolism; endogenous glyco-and lipo-proteins, damaged or * These authors contributed equally to this work. * * These authors are senior co-authors of this work. [4,5]. This phagocytic activity should be coupled to an alarm signal system that awakens other effector mechanisms of the immune system when the tissue damage cannot be controlled by the removal of the endogenous or exogenous molecules. To this end, the immune system has a myriad of specialized soluble or membrane-bound receptors called pattern recognition receptors (PRRs). These PRRs are non-polymorphic, nonclonally distributed, and germ-line encoded receptors recognizing microorganism-associated molecular patterns (MAMPs) -tha...

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The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Cited by 160 publications

References 418 publications

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

The class I scavenger receptor CD163 promotes internalization of ADAMTS13 by macrophages

The role of G protein-coupled receptors in the early evolution of neurotransmission and the nervous system

Exploiting scavenger receptors in cancer immunotherapy: Lessons from CD5 and SR‐B1

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