Calreticulin pp 248-257 | Cite as

Calreticulin in C. elegans

Part of the Molecular Biology Intelligence Unit book series (MBIU)


The nematode C. elegans is an ideal organism to study the in vivo genetic and biochemical functions of calreticulin. In vitro studies show that the C. elegans CRT-1 protein, like other calreticulins, is a calcium-binding molecular chaperone. Mutants of crt-1 in C. elegans mutants are viable and fertile, offering the opportunity for scientists to study in vivo functions of calreticulin at more depth, crt-1 null mutants showed temperature-sensitive fertility defects, and transcription of crt-1 was upregulated in stress conditions such as high temperature and ethanol treatment suggesting that calreticulin may be functioning in stress response. Mutants of the calreticulin gene were also shown to suppress necrotic cell death in neurons. The use of pharmological agents and the genetic application of mutants involved in ER calcium homeostasis showed that calreticulin was critical in the regulation of ER calcium levels during the neuronal degeneration process. Double mutants of crt-1 mutants and itr-1 IP3 receptor mutants displayed synergistic severity in defecation rhythm defects further suggesting the role of calreticulin in ER calcium homeostasis. Further genetic analysis in C. elegans between crt-1 and other components involved in ER calcium regulation should deepen our understanding of calreticulin and calcium homeostasis at both the cellular and organism level.


Double Mutant Calcium Homeostasis Necrotic Cell Death Fertility Defect Defecation Cycle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Michalak M, Corbett EF, Mesaeli N et al. Calreticulin: one protein, one gene, many functions. Biochem J 1999; 344:281–292.PubMedCrossRefGoogle Scholar
  2. 2.
    Brenner S. The genetics of Caenorhabditis elegans. Genetics 1974; 77:71–94.PubMedGoogle Scholar
  3. 3.
    Ostwald TJ, MacLennan DH. Isolation of a high affinity calcium-binding protein from sarcoplasmic reticulum. J Biol Chem 1974; 249:974–979.PubMedGoogle Scholar
  4. 4.
    The C. elegans Sequencing Consortium. (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 1998; 282:2012–2018.CrossRefGoogle Scholar
  5. 5.
    Wormbase home page:
  6. 6.
    Wood WB and the Community of C. elegans Researchers, eds. The Nematode Caenorhabditis elegans. Plainview; Cold Spring Harbor Laboratory Press, 1988.Google Scholar
  7. 7.
    Riddle DL, Blumenthal T, Meyer BJ et al, eds. C. elegans II. Plainview: Cold Spring Harbor Laboratory Press, 1997.Google Scholar
  8. 8.
    Epstein HE, Shakes DC, eds. Caenorhabditis elegans: Modern Biological Analysis of an Organisms. In: Methods in Cell Biology. Vol. 48. San Diego: Academic Press, 1995.Google Scholar
  9. 9.
    Smith MJ. A C. elegans gene encodes a protein homologous to mammalian calreticulin. DNA Seq 1992; 2:235–240.PubMedGoogle Scholar
  10. 10.
    Park B-J, Lee D-G, Yu J-R et al. Calreticulin, a Calcium-binding Molecular chaperone, Is Required for Stress Response and Fertility in Caenorhabditis elegans. Mol Biol Cell 2001; 12:2835–2845.PubMedGoogle Scholar
  11. 11.
    Saito Y, Ihara Y, Leqach MR, Cohen-Doyle MF et al. Calreticulin functions in vitro as a molecular chaperone for both glycosylated and non-glycosylated proteins. EMBO J 1999; 18:6718–6729.PubMedCrossRefGoogle Scholar
  12. 12.
    Barstead RJ. Reverse Genetics. In: Hope IA, ed. C. elegans: A Practical Approach. Oxford: Oxford University Press, 1999:97–118.Google Scholar
  13. 13.
    Park B-J, Lee JI, Lee J et al. Isolation of deletion mutants by reverse genetics in Caenorhabditis elegans. Korean J Biol Sci 2001; 5:65–69.CrossRefGoogle Scholar
  14. 14.
    Xu K, Tavernarakis N, Driscoll M. Necrotic Cell Death in C. elegans Requires the Function of Calreticulin and Regulators of Ca2+ Release from the Endoplasmic reticulum. Neuron 2001; 31:957–971.PubMedCrossRefGoogle Scholar
  15. 15.
    Mesaeli N, Nakamura K, Zvaritch E et al. Calreticulin is essential for cardiac development. J Cell Biol 1999; 144:857–868.PubMedCrossRefGoogle Scholar
  16. 16.
    Rauch F, Prudhomme J, Arabian A et al. Heart, brain, and body wall defects in mice lacking calreticulin. Exp Cell Res 2000; 256:105–111.PubMedCrossRefGoogle Scholar
  17. 17.
    Hong K, Driscoll M. A transmembrane domain of the putative channel subunit MEC-4 influences mechanotransduction and neurodegeneration in C. elegans. Genetics 1994; 116:377–388.Google Scholar
  18. 18.
    Adams CM, Snyder PM, Price MP et al. Protons activate brain Na+ channel 1 by inducing a conformational change that exposes a residue associated with neurodegeneration. J Biol Chem 1998; 273:30204–30207.PubMedCrossRefGoogle Scholar
  19. 19.
    Song SK, Karl IE, Ackerman JJ et al. Increased intracellular Ca2+: a critical link in the pathophysiology of sepsis? Proc Natl Acad Sci USA 1993; 90:3933–3937.PubMedCrossRefGoogle Scholar
  20. 20.
    Dal Santo P, Logan MA, Chisholm AD et al. The inositol trisphosphate receptor regulates a 50-sec-ond behavioral rhythm in C. elegans. Cell 1999; 98:757–767.CrossRefGoogle Scholar
  21. 21.
    Clandinin TR, DeModena JA, Sternberg PW. Inositol trisphospate mediates a Ras-independent response to LET-23 receptor tyrosine kinase activation in C. elegans. Cell 1998; 92:523–533.PubMedCrossRefGoogle Scholar
  22. 22.
    Grant B, Hirsh D. Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte. Mol Biol Cell 1999; 10:4311–4326.PubMedGoogle Scholar
  23. 23.
    Maryon EB, Coronado R, Anderson P. unc-68 encodes a ryanodine receptor involved in regulating C. elegans body-wall muscle contraction. J Cell Biol 1998; 134:885–893.CrossRefGoogle Scholar
  24. 24.
    Zwaal RR, Baelen KV, Groenen JT et al. The Sarco-Endoplasmic reticulum Ca2+ ATPase Is Required for Development and Muscle Function in Caenorhabditis elegans. J Biol Chem 2001; 276:43557–43563.PubMedCrossRefGoogle Scholar
  25. 25.
    Cho JH, Bandyopadhyay J, Lee J et al. Two isoforms of sarco/endoplasmic reticulum calcium ATPase (SERCA) are essential in Caenorhabditis elegans. Gene 2000; 261:211–219.PubMedCrossRefGoogle Scholar
  26. 26.
    Cho JH, Oh YS, Park KW et al. Calsequestrin, a calcium sequestering protein localized at the sarcoplasmic reticulum, is not essential for body-wall muscle function in Caenorhabditis elegans. J Cell Sci 2000; 113:3947–3958.PubMedGoogle Scholar
  27. 27.
    Liu LX, Spoerke JM, Mulligan EL et al. High-throughput isolation of Caenorhabditis elegans deletion mutants. Genome Res 1999; 9:859–867.PubMedCrossRefGoogle Scholar
  28. 28.
    Ranger AM, Grusby MJ, Hodge MR et al. The transcription factor NF-ATc is essential for cardiac valve formation. Nature 1998; 392:186–190.PubMedCrossRefGoogle Scholar
  29. 29.
    Molkentin JD, Lu JR, Antos CL et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 1998; 93:215–228.PubMedCrossRefGoogle Scholar
  30. 30.
    Graef IA, Chen F, Chen L et al. Signals transduced by Ca2+/calcineurin and NFATc3/c4 pattern the developing vasculature. Cell 2001; 105:863–875.PubMedCrossRefGoogle Scholar
  31. 31.
    Graef IA, Gastier JM, Francke U et al. Evolutionary relationships among Rem domains indicate functional diversification by recombination. PNAS 2001; 98:5740–5745.PubMedCrossRefGoogle Scholar
  32. 32.
    Bandyopadhyay J, Lee J, Lee J et al. Calcineurin, a calcium.calmodulin dependent phosphatase, is involved in movement, fertility, egg laying, and growth in C. elegans. Mol Biol Cell 2002; 13:3281–3293.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

There are no affiliations available

Personalised recommendations