BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Secreted decoy of insulin receptor is required for blood-brain and blood-retina barrier integrity in Drosophila

  • Jihyun Kim (Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University) ;
  • Nuri Choi (Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University) ;
  • Jeongsil Kim-Ha (Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University)
  • Received : 2022.12.19
  • Accepted : 2022.12.29
  • Published : 2023.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Glial cells play important roles during neurogenesis and in maintaining complex functions of the nervous system. Here, we report the characterization of a gene, Sdr, which contains a putative insulin-like growth factor receptor domain and is required to maintain critical nervous system functions in Drosophila. Sdr is expressed in glial cells during embryonic and larval stages of development, but its role in adult flies is poorly understood. As insulin signaling is important throughout the lifespan in human, we investigated the Sdr's role in adult flies. Our results demonstrate that Sdr is expressed on surface glial cells that surround the nervous system. Mutation of Sdr did not affect development but caused defects in locomotion and lifespan. Sdr mutants also showed increasingly severe defects in the blood-brain- and blood-retina-barriers as they aged. Therefore, we suggest a novel role of Sdr in maintaining the integrity of the blood-brain- and blood-retina-barriers in adult flies.

Keywords

Acknowledgement

This work was supported by grant NRF-2017R1D1A1B06029547 funded by the Ministry of Education, Science, and Technology of Korea to J. Kim-Ha.

References

  1. Clemmons DR (1997) Insulin-like growth factor binding proteins and their role in controlling IGF actions. Cytokine Growth Factor Rev 8, 45-62 https://doi.org/10.1016/S1359-6101(96)00053-6
  2. Smykal V, Pivarci M, Provaznik J et al (2020) Complex evolution of insect insulin receptors and homologous decoy receptors, and functional significance of their multiplicity. Mol Biol Evol 37, 1775-1789 https://doi.org/10.1093/molbev/msaa048
  3. Vorlova S, Rocco G, Lefave CV et al (2011) Induction of antagonistic soluble decoy receptor tyrosine kinases by intronic polyA activation. Mol Cell 43, 927-939 https://doi.org/10.1016/j.molcel.2011.08.009
  4. Levin BE and Sherwin RS (2011) Peripheral glucose homeostasis: does brain insulin matter? J Clin Invest 121, 3392-3395 https://doi.org/10.1172/JCI59653
  5. Chan O and Sherwin RS (2012) Hypothalamic regulation of glucose-stimulated insulin secretion. Diabetes 61, 564-565 https://doi.org/10.2337/db11-1846
  6. Myers MG and Olson DP (2012) Central nervous system control of metabolism. Nature 491, 357-363 https://doi.org/10.1038/nature11705
  7. Ziegler AN, Levison SW and Wood TL (2015) Insulin and IGF receptor signalling in neural-stem-cell homeostasis. Nat Rev Endocrinol 11, 161-170 https://doi.org/10.1038/nrendo.2014.208
  8. DeSalvo MK, Mayer N, Mayer F and Bainton RJ (2011) Physiologic and anatomic characterization of the brain surface glia barrier of Drosophila. Glia 59, 1322-1340 https://doi.org/10.1002/glia.21147
  9. Cui B and Cho SW (2022) Blood-brain barrier-on-a-chip for brain disease modeling and drug testing. BMB Rep 55, 213-219 https://doi.org/10.5483/BMBRep.2022.55.5.043
  10. Carro E, Nunez A, Busiguina S and Torres-Aleman I (2000) Circulating insulin-like growth factor I mediates effects of exercise on the brain. J Neurosci 20, 2926-2933 https://doi.org/10.1523/JNEUROSCI.20-08-02926.2000
  11. Russo VC, Gluckman PD, Feldman EL, and Werther GA (2005) The insulin-like growth factor system and its pleiotropic functions in brain. Endocr Rev 26, 916-943 https://doi.org/10.1210/er.2004-0024
  12. McDonell LM, Kernohan KD, Boycott KM and Sawyer SL (2015) Receptor tyrosine kinase mutations in developmental syndromes and cancer: two sides of the same coin. Hum Mol Genet 24, R60-R66 https://doi.org/10.1093/hmg/ddv254
  13. Petch LA, Harris J, Raymond VW, Blasband A, Lee DC and Earp HS (1990) A truncated, secreted form of the epidermal growth factor receptor is encoded by an alternatively spliced transcript in normal rat tissue. Mol Cell Biol 10, 2973-2982
  14. Garner AS and Large TH (1994) Isoforms of the avian TrkC receptor: a novel kinase insertion dissociates transformation and process outgrowth from survival. Neuron 13, 457-472 https://doi.org/10.1016/0896-6273(94)90360-3
  15. Obici S, Zhang BB, Karkanias G and Rossetti L (2002) Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 8, 1376-1382 https://doi.org/10.1038/nm1202-798
  16. Kleinridders A, Ferris HA, Cai W and Kahn CR (2014) Insulin action in brain regulates systemic metabolism and brain function. Diabetes 63, 2232-2243 https://doi.org/10.2337/db14-0568
  17. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M and Porte D Jr (1998) Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 50, 164-168 https://doi.org/10.1212/WNL.50.1.164
  18. Soto M, Cai W, Konishi M and Kahn CR (2019) Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior. Proc Natl Acad Sci U S A 116, 6379-6384 https://doi.org/10.1073/pnas.1817391116
  19. Plum L, Schubert M and Bruning JC (2005) The role of insulin receptor signaling in the brain. Trends Endocrinol Metab 16, 59-65 https://doi.org/10.1016/j.tem.2005.01.008
  20. Lopez-Lopez C, LeRoith D and Torres-Aleman I (2004) Insulin-like growth factor I is required for vessel remodeling in the adult brain. Proc Natl Acad Sci U S A 101, 9833-9838 https://doi.org/10.1073/pnas.0400337101
  21. Nishijima T, Piriz J, Duflot S et al (2010) Neuronal activity drives localized blood-brain-barrier transport of serum insulin-like growth factor-I into the CNS. Neuron 67, 834-846 https://doi.org/10.1016/j.neuron.2010.08.007
  22. Okamoto N, Nakamori R, Murai T, Yamauchi Y, Masuda A and Nishimura T (2013) A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. Genes Dev 27, 87-97 https://doi.org/10.1101/gad.204479.112
  23. Lin X and Smagghe G (2019) Roles of the insulin signaling pathway in insect development and organ growth. Peptides 122, 169923
  24. Garelli A, Gontijo AM, Miguela V, Caparros E and Dominguez M (2012) Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation. Science 336, 579-582 https://doi.org/10.1126/science.1216735
  25. Jaszczak JS, Wolpe JB, Bhandari R, Jaszczak RG and Halme A (2016) Growth coordination during Drosophila melanogaster imaginal disc regeneration is mediated by signaling through the relaxin receptor Lgr3 in the prothoracic gland. Genetics 204, 703-709 https://doi.org/10.1534/genetics.116.193706
  26. Zonta M, Angulo MC, Gobbo S et al (2003) Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 6, 43-50 https://doi.org/10.1038/nn980
  27. Kim J, Lee J, Lee S, Lee B and Kim-Ha J (2014) Phylogenetic comparison of oskar mRNA localization signals. Biochem Biophys Res Commun 444, 98-103 https://doi.org/10.1016/j.bbrc.2014.01.021