Phagocytic chimeric receptors require both transmembrane and cytoplasmic domains from the mannose receptor.

Kruskal, Benjamin A.; Sastry, Kedarnath N.; Warner, A.; Mathieu, Chantal; Ezekowitz, R. A. B.

doi:10.1084/jem.176.6.1673

Cited by 84 publications

(75 citation statements)

References 26 publications

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“…In particular, we determined whether their cytoplasmic tails alone or in combination with their transmembrane domains could, like known phagocytic receptors (2)(3)(4)(5), direct the phagocytosis of RBCs in a chimeric receptor system. In the case of known phagocytic receptors, notably IgG-Fc receptors, the tail domains are substrates for tyrosine kinases, and they recruit signaling proteins that mediate cytoskeletal rearrangement and membrane delivery to the phagocytic cup (1).…”

Section: Discussionmentioning

confidence: 99%

“…These signaling reactions are coordinated by the recruitment of actin-and membrane-related signal transduction molecules, including tyrosine kinases, by the cytoplasmic tails of these phagocytic receptors (1). Indeed, the cytoplasmic domains of the receptors mentioned above can trigger phagocytosis in chimeric receptors containing ectodomains from non-phagocytic receptors (2)(3)(4)(5).…”

mentioning

confidence: 99%

“…As alluded to above, the test is based upon the idea that phagocytic receptors contain amino acid sequences in their cytoplasmic tail, or tail plus transmembrane region, that are able to direct the uptake of large particles (e.g. red blood cells (RBCs)) using their own or heterologous ectodomains (2)(3)(4)(5). Our data show that whereas the LDL receptor fails this critical test, the cytoplasmic tail of LRP can, in fact, direct RBC phagocytosis in chimeric receptor model.…”

mentioning

confidence: 99%

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The Cytoplasmic Domain of the Low Density Lipoprotein (LDL) Receptor-related Protein, but Not That of the LDL Receptor, Triggers Phagocytosis

Patel

Morrow

Maxfield

et al. 2003

Journal of Biological Chemistry

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The macrophage LDL receptor and LDL receptor-related protein (LRP, CD91) mediate the phagocytic-like uptake of atherogenic lipoproteins and apoptotic cells, yet the structural basis of their phagocytic functions is not known. To address this issue, we transfected macrophages with chimeric proteins containing the cytoplasmic tails and transmembrane regions of the LDL receptor or LRP and the ectodomain of CD2, which can bind non-opsonized sheep red blood cells (SRBCs). Macrophages expressing receptors containing the LDL receptor domains were able to bind but not internalize SRBCs. In contrast, macrophages expressing receptors containing the cytoplasmic tail of LRP were able to bind and internalize SRBCs. Chimeras in which the LRP cytoplasmic tail was mutated in two di-leucine motifs and a tyrosine in an NPXYXXL motif were able to endocytose anti-CD2 antibody and bind SRBCs, but SRBC phagocytosis was decreased by 70%. Thus, the phagocytic-like functions of LRP, but not those of the LDL receptor, can be explained by the ability of the LRP cytoplasmic tail to trigger phagocytosis. These findings have important implications for atherogenesis and apoptotic cell clearance and for a fundamental cell biological understanding of how the LDL receptor and LRP function in internalization processes.The ability of macrophages to internalize large particles by the process known as phagocytosis represents a key property of this cell type (1). A variety of macrophage receptors have been demonstrated to mediate phagocytosis, including receptors that bind to the IgG-Fc domain, mannose residues, and complement after these molecules have opsonized cells. The process of phagocytosis involves a cascade of signaling reactions that orchestrate changes in the actin cytoskeleton and the delivery of internal membranes to the engulfing regions of the macrophage plasma membrane. These signaling reactions are coordinated by the recruitment of actin-and membrane-related signal transduction molecules, including tyrosine kinases, by the cytoplasmic tails of these phagocytic receptors (1). Indeed, the cytoplasmic domains of the receptors mentioned above can trigger phagocytosis in chimeric receptors containing ectodomains from non-phagocytic receptors (2-5).Certain members of the low density lipoprotein (LDL) 1 receptor family have been implicated in important phagocyticlike processes and have therefore been referred to as "phagocytic receptors." LDL receptor-related protein (LRP, CD91) has been reported to participate in the phagocytosis of apoptotic cells by macrophages (6 -8). In addition, LRP has been shown to play a role in the uptake of matrix-retained and aggregated LDL by macrophages and aggregated LDL by smooth muscle cells (9, 10). Moreover, work from a number of laboratories has shown that the LDL receptor itself mediates the uptake of large LDL aggregates (9,(11)(12)(13)(14)(15). The internalization of matrix-retained LDL by LRP and aggregated LDL by the LDL receptor are thought to contribute to the critical event of foam cell formation...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Cytoplasmic Domain of the Low Density Lipoprotein (LDL) Receptor-related Protein, but Not That of the LDL Receptor, Triggers Phagocytosis

Patel

Morrow

Maxfield

et al. 2003

Journal of Biological Chemistry

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“…a large extracellular region composed of an N-terminal cysteine-rich domain, a fibronectinlike type II domain, eight (30,35) or ten (37) repeats of a carbohydrate recognition domain (CRD), followed by a unique transmembrane domain and a short intracellular C-terminal domain. This latter domain contains a consensus sequence for the internalization of ligand-receptor complexes and is thought to confer to these receptors their endocytic properties (30,31,33,37,38).…”

Section: Receptor Essentially Via Crds 3-6mentioning

confidence: 99%

Identification of the Binding Domain for Secretory Phospholipases A2 on Their M-type 180-kDa Membrane Receptor

Nicolas¹,

Lambeau²,

Lazdunski³

1995

Journal of Biological Chemistry

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The rabbit muscle (M)-type receptor for secretory phospholipases A 2 (sPLA 2 s) has a large extracellular domain of 1394 amino acids, composed of an N-terminal cysteine-rich domain, a fibronectin-like type II domain, and eight carbohydrate recognition domains (CRDs). It is thought to mediate some of the physiological effects of mammalian sPLA 2 s, including vascular smooth muscle contraction and cell proliferation, and is able to internalize sPLA 2 s. Here, we show by site-directed mutagenesis that OS 1 , a snake venom sPLA 2 , binds to the receptor via its CRDs and that deletion of CRD 5 completely abolishes the binding of sPLA 2 s. Moreover, a receptor lacking all CRDs but CRD 5 was still able to bind OS 1 although with a lower affinity. Deletion of CRDs 4 and 6, surrounding the CRD 5, slightly reduced the affinity for OS 1 , thus suggesting that these CRDs are also involved in the binding of OS 1 . The M-type sPLA 2 receptor and the macrophage mannose receptor are homologous and are predicted to share the same tertiary structure. p-Aminophenyl-␣-D-mannopyranoside bovine serum albumin, a known ligand of the macrophage mannose receptor, binds to the M-type sPLA 2 receptor essentially via CRDs 3-6.

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“…J774E cells were plated in duplicate wells at 50-100% confluence on 24-well tissue culture plates 18 h before the experiment. Endocytosis was measured as previously described [16].…”

Section: Mannose-bsa Endocytosismentioning

confidence: 99%

Th1 and Th2 cytokines cooperate to stimulate mannose-receptor-mediated phagocytosis

Raveh

Kruskal

Farland

et al. 1998

Journal of Leukocyte Biology

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Abstract:The mannose receptor is a macrophage surface receptor that mediates both endocytosis and phagocytosis. Previous work has demonstrated that the prototypical T h 2 cytokine, interleukin-4 (IL-4), increases both cell-surface receptor expression and mannose receptor-mediated endocytosis, whereas the prototypical T h 1 cytokine, interferon-␥ (IFN-␥), decreases both surface expression and endocytosis. In many aspects of the immune response, T h 1 and T h 2 cytokines oppose each others' actions. We demonstrate that IL-4 and IFN-␥ alone and together enhance mannose receptor-mediated phagocytosis, despite opposing effects on cell-surface mannose receptor expression and endocytosis. Thus these usually antagonistic cytokines cooperate in increasing mannose receptor phagocytic function. The cooperative effect of these cytokines is not observed for Fc receptormediated phagocytosis. The T h 2 cytokine IL-13 exerts similar effects to IL-4. Our results suggest that T h 1 and T h 2 cytokines may act in concert at sites of inflammation to enhance mannose receptormediated phagocytosis of microorganisms. J. Leukoc. Biol. 64: 108-113; 1998.

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Phagocytic chimeric receptors require both transmembrane and cytoplasmic domains from the mannose receptor.

Cited by 84 publications

References 26 publications

The Cytoplasmic Domain of the Low Density Lipoprotein (LDL) Receptor-related Protein, but Not That of the LDL Receptor, Triggers Phagocytosis

The Cytoplasmic Domain of the Low Density Lipoprotein (LDL) Receptor-related Protein, but Not That of the LDL Receptor, Triggers Phagocytosis

Identification of the Binding Domain for Secretory Phospholipases A2 on Their M-type 180-kDa Membrane Receptor

Th1 and Th2 cytokines cooperate to stimulate mannose-receptor-mediated phagocytosis

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