The scavenger receptor CD36 plays a role in cytokine-induced macrophage fusion

Helming, Laura; Winter, Julia; Gordon, Siamon

doi:10.1242/jcs.037200

Cited by 131 publications

(119 citation statements)

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“…(DC-STAMP) and E-cadherin. 47,[67][68][69][70] It was proposed that these molecules may act as co-receptors for membrane attachment, as illustrated by the example of CD36, 69 or as chemokine receptors (e.g., DC-STAMP), 71 or they may trigger other yet unknown molecules that initiate the membrane fusion events.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Alternative activation of tumor-associated macrophages by IL-4

2010

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Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Alternative activation of tumor-associated macrophages by IL-4

2010

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“…CD36 acts as a facilitator of fatty acid uptake and is a receptor for a wide range of ligands including collagen, thrombospondin, anionic phospholipids, oxidized low density lipoprotein and erythrocytes parasitized with P. falciparum [6][7][8], and participate in macrophage fusion induced by IL-4 cytokines [9].…”

Section: Introductionmentioning

confidence: 99%

CD36 c.1264 T>G Null Mutation Impairs Acquisition of IgG Antibodies to Plasmodium falciparum MSP1‐₁₉ Antigen and is Associated with Higher Malaria Incidences in Tanzanian Children

et al. 2012

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Polymorphisms in genes that encode crucial signalling molecules have been proposed as factors that influence susceptibility to, and outcome of malaria. We studied the role of a mutation, c.1264 T>G, that causes CD36 deficiency on IgG responses to MSP‐119 antigen and malaria incidence. Children were genotyped for the c.1264 T>G mutation at the beginning of the study using PCR‐RFLP. IgG levels [optical density (OD) readings] and per cent seropositivity to MSP‐119 were determined at baseline by ELISA. Children were followed for 12 months for acquisition of anti‐MSP‐119 IgG antibody and malaria incidence. We observed a significant increase in the production of anti‐MSP‐119 IgG antibody in normal and heterozygous children during the 12 months of follow‐up, but not in homozygous mutants. Normal children had a significantly lower malaria incidence rate compared to other genotypes (χ2 = 115.59; P < 0.01). We conclude that the presence of the c.1264 T>G mutation that leads to CD36 deficiency is closely associated with reduced IgG production and higher malaria incidence. It is most likely that deficiency of CD36 which is known to modulate dendritic cell function suppresses the production of protective IgG antibodies directed to Plasmodium falciparum MSP‐119 antigen, which predisposes to the acquisition of clinical malaria in children.

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“…To determine where EFF-1 is required, we expressed a GFP-tagged version of this protein Furthermore, double mutants between eff-1 and psr-1 were no more defective than eff-1 mutants (Figure 2.2b), indicating that psr-1 and eff-1 are in the same genetic pathway. PSR-1 contains two highly conserved functional domains, an extracellular lysine-rich PS binding domain 21 , and an intracellular JmjC domain with multiple enzymatic activities [22][23][24] . We expressed different versions of full-length psr-1 cDNA selectively in the mechanosensory neurons of psr-1 mutant animals.…”

Section: Introduction and Resultsmentioning

confidence: 99%

“…We used the Squassh imaging tool (ImageJ) 24 to automatically select and measure these puncta. We found that increasing RAB-5 activity with RAB-5(CA) caused accumulation of EFF-1 within enlarged intracellular puncta (Figure 3.4a).…”

Section: Rab-5 Controls Eff-1 Localization To Intracellular Compartmentsmentioning

confidence: 99%

“…PS exposure and recognition by cell surface receptors is a common mechanism for many cell-cell fusion events, and has been implicated in the fusion of myoblasts 20,21 , syncytiotrophoblast cells in the placenta 22 , and macrophages 23,24 , as well as in the fusion that mediates the entry of some viruses into host cells 25,26 . Finally, it is likely that species-specific fusogens act as the last effectors in the mediation of membrane fusion.…”

Section: Axonal Fusion To Repair An Injured Axonmentioning

confidence: 99%

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Function and regulation of the fusogen EFF-1 during axonal repair

Linton¹

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In the current clinical environment, treatment options for nerve and spinal cord injuries remain limited. To develop novel therapies, we require a better understanding of axonal repair and its underlying molecular mechanisms. The response of an axon to a transection injury is complex: the axon still attached to the cell body begins a process of regenerative regrowth, whereas a concurrent process of degeneration is activated in the severed axonal fragment. Characterizing ways in which the axon can achieve repair, involving both regeneration and degeneration, is crucial to making progress in a clinical setting.We have studied a means of axonal repair called axonal fusion, which occurs spontaneously in the mechanosensory neurons of the nematode C. elegans. Following axotomy with a UV laser, the regrowing axonal fragment is able to directly fuse with its own severed fragment, re-establishing continuity. When axonal fusion was first described in C. elegans, the molecular pathways involved were unknown, and the only protein associated with the process was the fusogen Epithelial Fusion Failure-1 (EFF-1). EFF-1 is a nematode-specific transmembrane glycoprotein that acts to fuse plasma membranes. It has been studied extensively in other C. elegans tissues, but its function and regulation in neurons have been largely uncharacterized.In this context, we aimed to further understand the role of EFF-1 in axonal repair, focusing on its potential contribution to both regeneration and degeneration, and the mechanisms that regulate its fusogenic activity. We approached these biological questions using a combination of genetic and molecular biology techniques available in the C. elegans model system.The following chapters characterize EFF-1 function and regulation in the C. elegans mechanosensory neuron PLM. Firstly, we demonstrate a cell-autonomous role for EFF-1 in axonal fusion, and show that it has a dynamic localization pattern in the regenerating axon, whereby it is mobilized to the membrane of the regenerating growth cone. We also place it downstream in a pathway of apoptotic clearance molecules that allow recognition of the distal axonal fragment.Secondly, we find that neuronal EFF-1 is regulated by the endocytic GTPase RAB-5, with alterations in RAB-5 activity affecting both EFF-1 localization and its function in axonal fusion.Thirdly, we characterize the genes involved in the degeneration of the distal PLM axon following axotomy, and find a remarkable overlap with the molecules involved in regenerative fusion, possibly including EFF-1. Finally, we discuss an intriguing potential role for EFF-1 in mediating neuronal repair through cell-cell fusion. The research detailed here represents significant progress in understanding how a fusogen mediates axonal repair in vivo. It will potentially contribute to the application of axonal fusion as a novel therapy for patients with nerve injuries.ii Declaration by authorThis thesis is composed of my original work, and contains no material previously published or written by an...

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The scavenger receptor CD36 plays a role in cytokine-induced macrophage fusion

Cited by 131 publications

References 34 publications

Alternative activation of tumor-associated macrophages by IL-4

Alternative activation of tumor-associated macrophages by IL-4

CD36 c.1264 T>G Null Mutation Impairs Acquisition of IgG Antibodies to Plasmodium falciparum MSP1‐₁₉ Antigen and is Associated with Higher Malaria Incidences in Tanzanian Children

Function and regulation of the fusogen EFF-1 during axonal repair

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The scavenger receptor CD36 plays a role in cytokine-induced macrophage fusion

Cited by 131 publications

References 34 publications

Alternative activation of tumor-associated macrophages by IL-4

Alternative activation of tumor-associated macrophages by IL-4

CD36 c.1264 T>G Null Mutation Impairs Acquisition of IgG Antibodies to Plasmodium falciparum MSP1‐19 Antigen and is Associated with Higher Malaria Incidences in Tanzanian Children

Function and regulation of the fusogen EFF-1 during axonal repair

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CD36 c.1264 T>G Null Mutation Impairs Acquisition of IgG Antibodies to Plasmodium falciparum MSP1‐₁₉ Antigen and is Associated with Higher Malaria Incidences in Tanzanian Children