Isolation of a High Affinity Calcium-binding Protein from Sarcoplasmic Reticulum

Ostwald, Thomas J.; MacLennan, David H.

doi:10.1016/s0021-9258(19)43026-3

Cited by 357 publications

(47 citation statements)

References 25 publications

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“…The localization of calreticulin within the cell is broad and is still not completely clear. It is found in the ER/SR membranes (Ostwald and MacLennan, 1974) and seems to localize to the nucleus (Burns et al, 1994). It is also found on the surface of most mammalian cells (Arosa et al, 1999;Sadasivan et al, 1996;White et al, 1995) and was earlier shown to be identical to a key cellular receptor for C1q (Stuart et al, 1997).…”

Section: Introductionmentioning

confidence: 90%

Cell-Surface Calreticulin Initiates Clearance of Viable or Apoptotic Cells through trans-Activation of LRP on the Phagocyte

Gardai

McPhillips

Frasch

et al. 2005

Cell

1,262

1,246

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Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where "don't eat me" signals are rendered inactive and "eat me" signals, including calreticulin and phosphatidylserine, congregate together and signal for removal.

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Section: Introductionmentioning

confidence: 90%

Cell-Surface Calreticulin Initiates Clearance of Viable or Apoptotic Cells through trans-Activation of LRP on the Phagocyte

Gardai

McPhillips

Frasch

et al. 2005

Cell

1,262

1,246

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“…Calreticulin was first isolated by Ostwald and MacLennan in 1974 [26], followed by molecular cloning of the protein in 1989 by Smith and Koch [27] and Fliegel et al [28]. Since then, the protein has been extensively studied by many laboratories [29].…”

Section: Calreticulinmentioning

confidence: 99%

“…Calreticulin was originally identified as an ER\SR membrane protein [26]. Numerous studies confirmed ER localization of the protein in many diverse species, including plants [16,29,37,40,[83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99].…”

Section: Cellular Localization Of Calreticulinmentioning

confidence: 99%

Calreticulin: one protein, one gene, many functions

Michalak¹,

Corbett²,

Mesaeli³

et al. 1999

Biochem. J.

491

345

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The endoplasmic reticulum (ER) plays a critical role in the synthesis and chaperoning of membrane-associated and secreted proteins. The membrane is also an important site of Ca(2+) storage and release. Calreticulin is a unique ER luminal resident protein. The protein affects many cellular functions, both in the ER lumen and outside of the ER environment. In the ER lumen, calreticulin performs two major functions: chaperoning and regulation of Ca(2+) homoeostasis. Calreticulin is a highly versatile lectin-like chaperone, and it participates during the synthesis of a variety of molecules, including ion channels, surface receptors, integrins and transporters. The protein also affects intracellular Ca(2+) homoeostasis by modulation of ER Ca(2+) storage and transport. Studies on the cell biology of calreticulin revealed that the ER membrane is a very dynamic intracellular compartment affecting many aspects of cell physiology.

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“…and CALR account for 50-60% and 40-50%, respectively. Much is known about the JAK2 mechanism while the role of CALR remains obscure although it was discovered as a susceptible gene a long time ago [51]. CALR is a highly conserved protein bestowed mostly with negative charged amino acids such as aspartic acid (Asp) (13.2%) and galutamic acid (Glu) (12.9%) while exon-9 accounts for 21.2% and 37.90% (Figure S5D) of the two amino acids, respectively, a twofold increase in Asp and three-fold in Glu.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Connections between Calreticulin and Myeloproliferative Neoplasms via Calcium Signalling

Jaiswal

Wang

Zhu

et al. 2021

Preprint

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Mutations in the form of insertions and deletions (INDEL) in the calreticulin gene lead to essential thrombocythemia which is characterized by the formation of thrombosis. However, the connection between calreticulin INDEL and essential thrombocythemia remains largely elusive. Through combined molecular dynamics simulation and in-vitro studies on the wild type and mutated isoforms of calreticulin, the mechanism underlying the calreticulin INDEL induced essential thrombocythemia was investigated at the molecular level. Our results demonstrate that mutations in exon-9 could lead to significant conformational variations of calreticulin structure and thereby reducing its interaction with calcium ions due to decreased electrostatic contributions. The consequence of mutations on calreticulin’s structural integrity was revealed by identifying the key residues and their roles in calcium binding. Furthermore, mutations implemented by CRISPR-Cas9 in exon-9 showed diminished calcium signaling in HEK-293T cells, which agree well with our in-silico findings. The current study might help in understanding of the interactions between calreticulin exon-9 INDEL and calcium ions mediated by the structural variations of calreticulin. The results provide useful information for designing novel therapeutic approaches targeting essential thrombocythemia.

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Isolation of a High Affinity Calcium-binding Protein from Sarcoplasmic Reticulum

Cited by 357 publications

References 25 publications

Cell-Surface Calreticulin Initiates Clearance of Viable or Apoptotic Cells through trans-Activation of LRP on the Phagocyte

Cell-Surface Calreticulin Initiates Clearance of Viable or Apoptotic Cells through trans-Activation of LRP on the Phagocyte

Calreticulin: one protein, one gene, many functions

Unraveling the Connections between Calreticulin and Myeloproliferative Neoplasms via Calcium Signalling

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