Calreticulin and calnexin in the endoplasmic reticulum are important for phagocytosis

Müller‐Taubenberger, Annette

doi:10.1093/emboj/20.23.6772

Cited by 212 publications

(153 citation statements)

References 56 publications

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“…3) Mutants deficient in the ER proteins calreticulin and calnexin are deficient in phagocytosis. Moreover, green-fluorescent protein-labeled calreticulin and calnexin demonstrated a link between the ER and phagocytic cup (50). Thus, we suggest that a strand of the ER mediates the line of communication indicated by the present study.…”

Section: Discussionsupporting

confidence: 69%

Intracellular Calcium Waves Accompany Neutrophil Polarization, Formylmethionylleucylphenylalanine Stimulation, and Phagocytosis: A High Speed Microscopy Study

Kindzelskii

Petty

2003

The Journal of Immunology

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Using high sensitivity fluorescence imaging with shutter speeds ∼600,000 times faster than those of video frames, we have characterized Ca2+ waves within cells in exquisite detail to reveal Ca2+ signaling routes. Polarized neutrophils exhibited a counterclockwise rotating ryanodine-sensitive juxtamembrane Ca2+ wave during temporal calcium spikes. During stimulation with fMLP, a chemotactic factor, two Ca2+ waves traveling in opposite directions around the perimeter of the cell emanated from sites of stimulation (the clockwise wave is verapamil sensitive). Phagocytosed targets exhibit counterclockwise Ca2+ waves traveling about their periphery originating from the plasma membrane. This study: 1) outlines the technology to observe Ca2+ signaling circuitry within small living cells; 2) shows that extracellular spatial information in the form of a chemotactic factor gradient is transduced into intracellular chemical patterns, which provides fresh insights in signaling; 3) suggests that a line of communication exits between the cell surface and phagosomes; and 4) suggests that spatiotemporal Ca2+ patterns contribute to drug actions.

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Section: Discussionsupporting

confidence: 69%

Intracellular Calcium Waves Accompany Neutrophil Polarization, Formylmethionylleucylphenylalanine Stimulation, and Phagocytosis: A High Speed Microscopy Study

Kindzelskii

Petty

2003

The Journal of Immunology

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“…Recent studies have suggested that the ER participates in phagocytosis. Recruitment of ER to the site of phagocytosis has been suggested by studies showing the presence of ER-associated proteins on purified phagosomes (12) and the accumulation of GFP-labeled calreticulin and calnexin, two proteins of the ER, at the phagocytic cup (26). In addition, electron microscopy studies indicate that phagosomes maintain a thin filament of ER connecting them with the plasma membrane (27).…”

Section: Discussionmentioning

confidence: 98%

Signal sequence within FcγRIIA controls calcium wave propagation patterns: Apparent role in phagolysosome fusion

Worth

Kim²,

Kindzelskii³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Calcium oscillations and traveling calcium waves have been observed in living cells, although amino acid sequences regulating wave directionality and downstream cell functions have not been reported. In this study we identify an amino acid sequence within the cytoplasmic domain of the leukocyte IgG receptor Fc␥RIIA that affects the amplitude of calcium spikes and the spatiotemporal dynamics of calcium waves in the vicinity of phagosomes. By using high-speed microscopy to map calcium-signaling routes within cells, we have discovered that bound IgG-coated targets trigger two calcium waves traveling in opposite directions about the perimeter of cells expressing Fc␥RIIA. After phagocytosis, one calcium wave propagates around the plasma membrane to the site of phagocytosis where it splits into two calcium signals: one traveling to and encircling the phagosome once, and the second continuing around the plasma membrane to the point of origin. However, in a genetically engineered form of Fc␥RIIA containing a mutation in the cytoplasmic L-T-L motif, the calcium signal travels around the plasma membrane, but is not properly routed to the phagosome. Furthermore, these calcium pattern-deficient mutants were unable to support phagolysosome fusion, although recruitment of phagolysosome-associated proteins lysosome-associated protein 1, Rab5, and Rab7 were normal. Our findings suggest that: (i) calcium signaling is a late step in phagolysosome fusion, (ii) a line of communication exists between the plasma membrane and phagosome, and (iii) the L-T-L motif is a signal sequence for calcium signal routing to the phagosome.

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“…For example, in Dictyostelium cells, calreticulin and calnexin are important for yeast particle phagocytosis. 20 Moreover, calreticulin has been identified as a marker for engulfment of apoptotic cells by Drosophila phagocytes. 21 Since calreticulin is detected on the surface of apoptotic cells as well as on phagocytes, 22 several modes of action for calreticulin have been proposed to explain its role in engulfment.…”

Section: Positive Regulators Of Uptake Dying Cellmentioning

confidence: 99%

From regulation of dying cell engulfment to development of anti-cancer therapy

Krysko

Vandenabeele

2007

Cell Death Differ

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Cell death and efficient engulfment of dying cells ensure tissue homeostasis and is involved in pathogenesis. Clearance of dying cells is a complex and dynamic process coordinated by interplay between ligands on dying cell, bridging molecules, and receptors on engulfing cells. In this review, we will discuss recent advances and significance of molecular changes on the surface of dying cells implicated in their recognition and clearance as well as factors released by dying cells that attract macrophages to the site of cell death. It is now becoming apparent that phagocytes use a specific set of mechanisms to discriminate between live and dead cells, and this phenomenon will be illustrated here. Next, we will discuss potential mechanisms by which removal of dying cells could modulate immune responses of phagocytes, in particular of macrophages. Finally, we will address possible strategies for manipulating the immunogenicity of dying cells in experimental cancer therapies.

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Calreticulin and calnexin in the endoplasmic reticulum are important for phagocytosis

Cited by 212 publications

References 56 publications

Intracellular Calcium Waves Accompany Neutrophil Polarization, Formylmethionylleucylphenylalanine Stimulation, and Phagocytosis: A High Speed Microscopy Study

Intracellular Calcium Waves Accompany Neutrophil Polarization, Formylmethionylleucylphenylalanine Stimulation, and Phagocytosis: A High Speed Microscopy Study

Signal sequence within FcγRIIA controls calcium wave propagation patterns: Apparent role in phagolysosome fusion

From regulation of dying cell engulfment to development of anti-cancer therapy

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