Calreticulin Couples Calcium Release and Calcium Influx in Integrin-mediated Calcium Signaling

Kwon, Min Seong; Park, Chun Shik; Choi, Kyeong-Rock; Park, Chul–Seung; Ahnn, Joohong; Kim, Jae Il; Eom, Soo Hyun; Kaufman, Stephen J.; Song, Woo Keun

doi:10.1091/mbc.11.4.1433

Cited by 113 publications

(81 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The pattern of ligand-induced calcium influx followed by intracellular store release is typical of integrin effects on [Ca 2+ ]i in non-neuronal cells (Bhattacharya et al, 2000;Kwon et al, 2000;Schottelndreier et al, 2001). Moreover, when examined, influx is generally found to be mediated by VSCCs and dependent upon tyrosine kinase signaling (i.e., blocked by genistein) (Wu et al, 1998;Kwon et al, 2000;Wu et al, 2001).…”

Section: Discussionmentioning

confidence: 94%

“…Moreover, when examined, influx is generally found to be mediated by VSCCs and dependent upon tyrosine kinase signaling (i.e., blocked by genistein) (Wu et al, 1998;Kwon et al, 2000;Wu et al, 2001). What distinguishes effects in neurons is the participation of neuron-specific receptors that produce depolarization (AMPA receptors) and voltage-dependent influx (e.g., NMDA receptors).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Lin

Hilgenberg

Smith

et al. 2008

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Integrins regulate cytoplasmic calcium levels ([Ca 2+ ]i) in various cell types but information on activities in neurons is limited. The issue is of current interest because of evidence that both integrins and changes in [Ca 2+ ]i are required for Long-Term Potentiation. Accordingly, the present studies evaluated integrin ligand effects in cortical neurons. Integrin ligands or α5ß1 integrin activating antisera rapidly increased [Ca 2+ ]i with effects greater in glutamatergic than GABAergic neurons, absent in astroglia, and blocked by ß1 integrin neutralizing antisera and the tyrosine kinase antagonist genistein. Increases depended upon extracellular calcium and intracellular store release. Ligandinduced effects were reduced by voltage-sensitive calcium channel and NMDA receptor antagonists, but blocked by tetrodotoxin or AMPA receptor antagonists. These results indicate that integrin ligation triggers AMPA receptor/depolarization-dependent calcium influx followed by intracellular store release and suggest the possibility that integrin modulation of activity-induced changes in [Ca 2+ ]i contributes importantly to lasting synaptic plasticity in forebrain neurons.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Lin

Hilgenberg

Smith

et al. 2008

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

show abstract

“…Vinculin and ␣-actinin, but not the ␣ v ␤ 3 integrin, are selectively redistributed from the restructured focal adhesions in response to thrombospondin (5,8). A 19-amino acid sequence (amino acids [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] in the N-terminal heparin-binding domains of both TSP-1 and TSP-2, referred to as the hep I peptide, has been determined to be sufficient for focal adhesion disassembly (9). The signaling events stimulated by thrombospondin/hep I interactions with cells are only partially understood.…”

Section: Thrombospondin (Tsp)mentioning

confidence: 99%

Thrombospondin Mediates Focal Adhesion Disassembly through Interactions with Cell Surface Calreticulin

Goicoechea¹,

Orr²,

Pallero³

et al. 2000

Journal of Biological Chemistry

155

135

View full text Add to dashboard Cite

Thrombospondin induces reorganization of the actin cytoskeleton and restructuring of focal adhesions. This activity is localized to amino acids 17-35 in the N-terminal heparin-binding domain of thrombospondin and can be replicated by a peptide (hep I) with this sequence. Thrombospondin/hep I stimulate focal adhesion disassembly through a mechanism involving phosphoinositide 3-kinase activation. However, the receptor for this thrombospondin sequence is unknown. We now report that calreticulin on the cell surface mediates focal adhesion disassembly by thrombospondin/hep I. A 60-kDa protein from endothelial cell detergent extracts has homology and immunoreactivity to calreticulin, binds a hep I affinity column, and neutralizes thrombospondin/ hep I-mediated focal adhesion disassembly. Calreticulin on the cell surface was confirmed by biotinylation, confocal microscopy, and by fluorescence-activated cell sorting analyses. Thrombospondin and calreticulin potentially bind through the hep I sequence, since thrombospondin-calreticulin complex formation can be blocked specifically by hep I peptide. Antibodies to calreticulin and preincubation of thrombospondin/hep I with glutathione S-transferase-calreticulin block thrombospondin/hep I-mediated focal adhesion disassembly and phosphoinositide 3-kinase activation, suggesting that calreticulin is a component of the thrombospondin-induced signaling cascade that regulates cytoskeletal organization. These data identify both a novel receptor for the N terminus of thrombospondin and a distinct role for cell surface calreticulin in cell adhesion.

show abstract

mentioning

confidence: 99%

“…5,7 CRT is a Ca 2 þ -binding protein with two sites (with high and low capacity) for buffering Ca 2 þ , thus affecting Ca 2 þ signaling and Ca 2 þ homeostasis. [8][9][10] CRT is a soluble protein that is mainly located in the lumen of the endoplasmic reticulum (ER) where it also functions as a chaperone and a lectin interacting with several proteins endowed with disulfide isomerase activity, in particular ERp57. 11,12 A fraction of CRT resides outside of the ER, where it has been suggested to regulate nuclear protein transport, 13 signaling via nuclear steroid receptors 14 and integrin signaling.…”

mentioning

confidence: 99%

The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death

et al. 2008

View full text Add to dashboard Cite

The exposure of calreticulin (CRT) on the plasma membrane can precede anthracycline-induced apoptosis and is required for cell death to be perceived as immunogenic. Mass spectroscopy, immunofluorescence and immunoprecipitation experiments revealed that CRT co-translocates to the surface with another endoplasmic reticulum-sessile protein, the disulfide isomerase ERp57. The knockout and knockdown of CRT or ERp57 inhibited the anthracycline-induced translocation of ERp57 or CRT, respectively. CRT point mutants that fail to interact with ERp57 were unable to restore ERp57 translocation upon transfection into crt À/À cells, underscoring that a direct interaction between CRT and ERp57 is strictly required for their co-translocation to the surface. ERp57 low tumor cells generated by retroviral introduction of an ERp57-specific shRNA exhibited a normal apoptotic response to anthracyclines in vitro, yet were resistant to anthracycline treatment in vivo. Moreover, ERp57 low cancer cells (which failed to expose CRT) treated with anthracyclines were unable to elicit an anti-tumor response in conditions in which control cells were highly immunogenic. The failure of ERp57 low cells to elicit immune responses and to respond to chemotherapy could be overcome by exogenous supply of recombinant CRT protein. These results indicate that tumors that possess an intrinsic defect in the CRT-translocating machinery become resistant to anthracycline chemotherapy due to their incapacity to elicit an anticancer immune response. The conventional treatment of cancer relies upon radiotherapy and chemotherapy, two procedures that supposedly mediate their therapeutic effects solely by intrinsic mechanisms of tumor cell death and without direct participation by the host immune system. Nevertheless, there are specific circumstances in which conventional anti-cancer treatments can induce a modality of cell death that is immunogenic, whereby dying cells elicit a tumor-specific immune response culminating in elimination of tumor cells. Although most chemotherapeutic agents kill tumor cells through a morphologically indistinguishable apoptotic pathway, they differ in their capacity to stimulate immunogenic as opposed to nonimmunogenic cell death. 1 Recently, we reported that tumor cells undergoing immunogenic cell death translocate intracellular calreticulin (endo-CRT) to their plasma membrane (PM) surface (ecto-CRT), facilitating tumor cell recognition and engulfment by dendritic cells (DC) and subsequent T-cellmediated elimination of the tumor. 2 Accordingly, anthracyclines and g-irradiation, which elicit immunogenic cell death, induce CRT exposure whereas other proapoptotic agents that induce non-immunogenic cell death fail to induce ecto-CRT. [2][3][4] Depletion of CRT abolishes the immunogenicity of cell death elicited by anthracyclines, whereas addition of exogenous CRT or enforced surface exposure of CRT by pharmacological agents that favor CRT translocation can enhance the immunogenicity of cell death. 2,4 An additional signal emitted during ...

show abstract

Calreticulin Couples Calcium Release and Calcium Influx in Integrin-mediated Calcium Signaling

Cited by 113 publications

References 54 publications

Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Integrin regulation of cytoplasmic calcium in excitatory neurons depends upon glutamate receptors and release from intracellular stores

Thrombospondin Mediates Focal Adhesion Disassembly through Interactions with Cell Surface Calreticulin

The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death

Contact Info

Product

Resources

About