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ITR-1

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ITR-1 is a gene found in a small worm called Caenorhabditis elegans (C. elegans). This gene encodes a protein called the inositol 1,4,5-trisphosphate receptor (IP3 receptor), which plays a key role in calcium signaling inside cells[1]. Calcium signals are important for many processes in the worm, including development, movement, and how its cells function.

History and Discovery

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Researchers discovered ITR-1 while investigating how cells in C. elegans respond to signals that control calcium levels. One important molecule in this process is IP3, which tells certain parts of the cell to release stored calcium[2]. The ITR-1 gene was found to produce the receptor that responds to IP3, acting like a gate that opens to let calcium out.

The discovery of ITR-1 was important because it showed that calcium signaling is a conserved system, meaning it's been used by many organisms throughout evolution, not just worms. It also helped scientists understand how internal signals in cells can control larger processes like development and behavior[2].

Function

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The ITR-1 gene encodes a protein that functions as an IP3-gated calcium channel, mediating the release of calcium ions from intracellular stores. Calcium signaling through ITR-1 is essential for multiple biological processes, including:

Role in development

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In C elegans, ITR-1 is involved in several key developmental pathways:

  • Germline Development: ITR-1 mediated calcium singaling is required for proper germ cell maturation and fertilization.
  • Neuronal Functions: ITR-1 contributes to synaptic plasticity and behavioral responses, influencing locomotion and sensory perception[5].
  • Organ Formation: Regulates pharyngeal and intestinal function during larval stages[3].

Genetic regulation

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The expression of ITR-1 is tightly regulated by upstream signaling pathways, including:

Experimental Studies

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Several studies have explored the function of ITR-1 through genetic knockouts, RNA interference (RNAi), and calcium imaging techniques. Key findings include:

  • Loss of function mutations result in defects in defecation rhythym and germ cell proliferation[4].
  • Overactivation of ITR-1 can lead to uncoordinated locomotion and disrupted neuronal signaling.
  • Pharmacological inhibition of ITR-1 impairs egg-laying and reproductive fitness in C. elegans.

Homology and Evolution

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  • ITPR1 (humans): involved in neurodevelopment and calcium homeostasis
  • ITPR2 and ITPR3 (humans): Regulating cell proliferation and apoptosis
  1. ^ a b Dal Santo, P.; Logan, M. A.; Chisholm, A. D.; Jorgensen, E. M. (1999-09-17). "The inositol trisphosphate receptor regulates a 50-second behavioral rhythm in C. elegans". Cell. 98 (6): 757–767. doi:10.1016/s0092-8674(00)81510-x. ISSN 0092-8674. PMID 10499793.
  2. ^ a b Walker, Denise S.; Gower, Nicholas J. D.; Ly, Sung; Bradley, Gemma L.; Baylis, Howard A. (2002-04). "Regulated disruption of inositol 1,4,5-trisphosphate signaling in Caenorhabditis elegans reveals new functions in feeding and embryogenesis". Molecular Biology of the Cell. 13 (4): 1329–1337. doi:10.1091/mbc.01-08-0422. ISSN 1059-1524. PMC 102272. PMID 11950942. {{cite journal}}: Check date values in: |date= (help)
  3. ^ a b Avery, L. (1993-04). "The genetics of feeding in Caenorhabditis elegans". Genetics. 133 (4): 897–917. doi:10.1093/genetics/133.4.897. ISSN 0016-6731. PMC 1205408. PMID 8462849. {{cite journal}}: Check date values in: |date= (help)
  4. ^ a b Teramoto, Takayuki; Iwasaki, Kouichi (2006-09-01). "Intestinal calcium waves coordinate a behavioral motor program in C. elegans". Cell Calcium. 40 (3): 319–327. doi:10.1016/j.ceca.2006.04.009. ISSN 0143-4160.
  5. ^ a b Baylis, H. A.; Furuichi, T.; Yoshikawa, F.; Mikoshiba, K.; Sattelle, D. B. (1999-11-26). "Inositol 1,4,5-trisphosphate receptors are strongly expressed in the nervous system, pharynx, intestine, gonad and excretory cell of Caenorhabditis elegans and are encoded by a single gene (itr-1)". Journal of Molecular Biology. 294 (2): 467–476. doi:10.1006/jmbi.1999.3229. ISSN 0022-2836. PMID 10610772.
  6. ^ Berridge, M. J. (1993-01-28). "Inositol trisphosphate and calcium signalling". Nature. 361 (6410): 315–325. doi:10.1038/361315a0. ISSN 0028-0836. PMID 8381210.
  7. ^ Foskett, J. Kevin; White, Carl; Cheung, King-Ho; Mak, Don-On Daniel (2007-04). "Inositol trisphosphate receptor Ca2+ release channels". Physiological Reviews. 87 (2): 593–658. doi:10.1152/physrev.00035.2006. ISSN 0031-9333. PMC 2901638. PMID 17429043. {{cite journal}}: Check date values in: |date= (help)