CRC (Drosophila melanogaster)
Description [+]
- Synonyms: CRC, CALRETICULIN
- Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
- Short gene description: Calreticulin
- Family: other
- Process: apoptosis,
- Pathways: apoptotic cell clearance,
- Criteria: manually curated
- Curator comment: Null
- Human ortholog(s): CALR CALR3
- WIKI: CRC-D_melanogaster
References [+]
- Identification of calreticulin as a marker for phagocytosis of apoptotic cells in Drosophila.
- Kuraishi T, Manaka J, Kono M, Ishii H, Yamamoto N, Koizumi K, Shiratsuchi A, Lee BL, Higashida H, Nakanishi Y
- Apoptotic cell phagocytosis is initiated through the specific interaction between markers for phagocytosis present at the surface of targets and their receptors of phagocytes. Although many molecules have been proposed to be phagocytosis markers and receptors in mammals, information as to the identity of those molecules is limited for invertebrate animals. Calreticulin, a molecular chaperone that functions in the lumen of the endoplasmic reticulum, was recently reported to be the second general marker, the membrane phospholipid phosphatidylserine being the first, for mammalian apoptotic cells to be recognized by phagocytes. We here asked whether or not calreticulin serves as a marker for phagocytosis in Drosophila. Phagocytosis of apoptotic S2 cells by Drosophila hemocyte-derived l(2)mbn cells, which we previously showed to occur independent of phosphatidylserine, was inhibited by the addition of anti-calreticulin antibody. This inhibition was observed when the target cells, but not phagocytes, were pre-incubated with the antibody. In addition, RNA interference-mediated reduction of calreticulin expression in apoptotic S2 cells, but not in l(2)mbn cells, reduced the level of phagocytosis. An immunocytochemical analysis revealed that calreticulin is widely distributed at the surface of viable S2 cells. After the induction of apoptosis, cell surface calreticulin seemed to form aggregates, with no change in its amount. Furthermore, in embryos of a mutant Drosophila strain that expresses calreticulin at a reduced level, the level of phagocytosis of apoptotic cells was about a half of that observed in embryos of a wild-type strain. These results collectively indicate that calreticulin is the first molecule to be identified as a marker for phagocytosis of apoptotic cells by Drosophila phagocytes. Exp Cell Res. 2007 Feb 1;313(3):500-10. Epub 2006 Nov 1.
- Clearance of apoptotic corpses.
- Fullard JF, Kale A, Baker NE
- Apoptotic corpses can be engulfed and cleared by many other cell types in addition to 'professional' phagocytes such as macrophage. Studies of several organisms have contributed to the understanding of apoptotic corpse engulfment. Two partially redundant engulfment pathways have been characterized that act even in non-professional phagocytes to promote corpse engulfment. This review summarizes some recent progress in signaling by these pathways, including the exposure of eat-me-signals on apoptotic cells, and insights from Drosophila on the roles of the bridging receptor Six Microns Under, the non-receptor tyrosine kinase Shark, and store-operated calcium release in the Draper/Ced-1 pathway of corpse recognition and internalization. The mechanism of apoptotic phagosome maturation is outlined, and possible connections between corpse engulfment and proliferation, cell competition, and immunity are discussed. Apoptosis. 2009 Aug;14(8):1029-37.
- References from Human ortholog(s):
- Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.
- Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM
- 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. Cell. 2005 Oct 21;123(2):321-34.
- Apoptosis: controlled demolition at the cellular level.
- Taylor RC, Cullen SP, Martin SJ
- Apoptosis is characterized by a series of dramatic perturbations to the cellular architecture that contribute not only to cell death, but also prepare cells for removal by phagocytes and prevent unwanted immune responses. Much of what happens during the demolition phase of apoptosis is orchestrated by members of the caspase family of cysteine proteases. These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules. Nat Rev Mol Cell Biol. 2008 Mar;9(3):231-41.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Calreticulin | 21 | 332 |
Protein sequence [+]
Crc | Drosophila melanogaster | 7227 | length:406
MMWCKTVIVLLATVGFISAEVYLKENFDNENWEDTWIYSKHPGKEFGKFVLTPGTFYNDA
EADKGIQTSQDARFYAASRKFDGFSNEDKPLVVQFSVKHEQNIDCGGGYVKLFDCSLDQT
DMHGESPYEIMFGPDICGPGTKKVHVIFSYKGKNHLISKDIRCKDDVYTHFYTLIVRPDN
TYEVLIDNEKVESGNLEDDWDFLAPKKIKDPTATKPEDWDDRATIPDPDDKKPEDWDKPE
HIPDPDATKPEDWDDEMDGEWEPPMIDNPEFKGEWQPKQLDNPNYKGAWEHPEIANPEYV
PDDKLYLRKEICTLGFDLWQVKSGTIFDNVLITDDVELAAKAAAEVKNTQAGEKKMKEAQ
DEVQRKKDEEEAKKASDKDDEDEDDDDEEKDDESKQDKDQSEHDEL
EADKGIQTSQDARFYAASRKFDGFSNEDKPLVVQFSVKHEQNIDCGGGYVKLFDCSLDQT
DMHGESPYEIMFGPDICGPGTKKVHVIFSYKGKNHLISKDIRCKDDVYTHFYTLIVRPDN
TYEVLIDNEKVESGNLEDDWDFLAPKKIKDPTATKPEDWDDRATIPDPDDKKPEDWDKPE
HIPDPDATKPEDWDDEMDGEWEPPMIDNPEFKGEWQPKQLDNPNYKGAWEHPEIANPEYV
PDDKLYLRKEICTLGFDLWQVKSGTIFDNVLITDDVELAAKAAAEVKNTQAGEKKMKEAQ
DEVQRKKDEEEAKKASDKDDEDEDDDDEEKDDESKQDKDQSEHDEL
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL011773-PA | orthology | Aedes |
| A_aegypti_AAEL001005-PA | orthology | Aedes |
| A_gambiae_AGAP004212-PA | orthology | Anopheles |
| IPI00597616.2 | orthology | Chicken |
| XR_024426.1 | orthology | Chimpanzee |
| XR_022389.1 | orthology | Chimpanzee |
| NA | orthology | Ciona |
| CALR3_BOVIN | orthology | Cow |
| IPI00716596.5 | orthology | Cow |
| CALR_BOVIN | orthology | Cow |
| CALR3 | orthology | Dog |
| CALR | orthology | Dog |
| CALR | orthology | Fugu |
| CALR3 | orthology | Fugu |
| CALR3 (2 of 2) | orthology | Gasterosteus |
| CALR | orthology | Gasterosteus |
| CALR3 (1 of 2) | orthology | Gasterosteus |
| CALR | orthology | Gorilla |
| XP_001494051.2 | orthology | Horse |
| CALR3 | orthology | Horse |
| CALR | orthology | Horse |
| CALR | orthology | Human |
| CALR3 | orthology | Human |
| CALR | orthology | Lyzard |
| CALR | orthology | Macaca |
| M_mulatta_ENSMMUP00000040204 | orthology | Macaca |
| CALR | orthology | Medaka |
| CALR3 (2 of 2) | orthology | Medaka |
| CALR3 (1 of 2) | orthology | Medaka |
| CALR | orthology | Monodelphis |
| XM_001372298.1 | orthology | Monodelphis |
| CALR3 | orthology | Monodelphis |
| Calr4 | orthology | Mouse |
| Calr | orthology | Mouse |
| Calr3 | orthology | Mouse |
| CALR3 | orthology | Orangutan |
| CALR | orthology | Orangutan |
| CALR | orthology | Ornithorhynchus |
| O_anatinus_ENSOANP00000023446 | orthology | Ornithorhynchus |
| CALR3 | orthology | Ornithorhynchus |
| CALR3 | orthology | Rabbit |
| Calr4 | orthology | Rat |
| NP_001012212.1 | orthology | Rat |
| CALR_RAT | orthology | Rat |
| CALR | orthology | Tetraodon |
| crt-1 | orthology | Worm |
| CALR3 | orthology | Xenopus |
| calr | orthology | Xenopus |
| CALR (1 of 3) | orthology | Zebrafish |
| calr | orthology | Zebrafish |
| calrl | orthology | Zebrafish |
| A_aegypti_AAEL015100-PA | paralogy | Aedes |
| A_gambiae_AGAP005032-PA | paralogy | Anopheles |
| IPI00580922.2 | paralogy | Chicken |
| NP_001025791.1 | paralogy | Chicken |
| CLGN | paralogy | Chimpanzee |
| CANX | paralogy | Chimpanzee |
| NA | paralogy | Ciona |
| CLGN_BOVIN | paralogy | Cow |
| CLGN | paralogy | Dog |
| CALX_CANFA | paralogy | Dog |
| Cnx99A | paralogy | Fly |
| CG9906 | paralogy | Fly |
| CG1924 | paralogy | Fly |
| CLGN | paralogy | Fugu |
| CANX | paralogy | Fugu |
| CLGN | paralogy | Gasterosteus |
| CANX | paralogy | Gasterosteus |
| CANX | paralogy | Gorilla |
| CANX | paralogy | Horse |
| CLGN | paralogy | Horse |
| CANX | paralogy | Human |
| CLGN | paralogy | Human |
| CANX | paralogy | Lyzard |
| CLGN | paralogy | Lyzard |
| CANX | paralogy | Macaca |
| CLGN | paralogy | Macaca |
| CLGN | paralogy | Medaka |
| CANX | paralogy | Medaka |
| M_domestica_ENSMODP00000020352 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000019327 | paralogy | Monodelphis |
| CLGN | paralogy | Monodelphis |
| XR_030339.1 | paralogy | Monodelphis |
| Canx | paralogy | Mouse |
| Clgn | paralogy | Mouse |
| CANX | paralogy | Orangutan |
| CLGN | paralogy | Orangutan |
| CANX | paralogy | Ornithorhynchus |
| CLGN | paralogy | Ornithorhynchus |
| CLGN | paralogy | Rabbit |
| CANX | paralogy | Rabbit |
| CALX_RAT | paralogy | Rat |
| NP_001102942.1 | paralogy | Rat |
| CLGN | paralogy | Tetraodon |
| CANX (1 of 2) | paralogy | Tetraodon |
| CANX (2 of 2) | paralogy | Tetraodon |
| cnx-1 | paralogy | Worm |
| canx | paralogy | Xenopus |
| CLGN | paralogy | Xenopus |
| CNE1 | paralogy | Yeast |
| CLGN | paralogy | Zebra finch |
| CANX | paralogy | Zebra finch |
| clgn | paralogy | Zebrafish |
| CANX (2 of 2) | paralogy | Zebrafish |
| canx | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0007154 | cell communication | biological_proccess | IEA |
| GO:0007165 | signal transduction | biological_proccess | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0035091 | phosphoinositide binding | mollecular_function | IEA |
Check GO Evidence Codes here
Information from other databases [+]
- Ensembl genome browser [?] : FBgn0005585
- Expression info from Arrayexpress [?] : FBgn0005585
- Protein expression from Protein Atlas: [?] FBgn0005585
Click on [?] for more information.
