Calreticulin in C. elegans
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.
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