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Characterization of an Aplysia vasotocin signaling system and actions of posttranslational modifications and individual residues of the ligand on receptor activity.
Xu, Ju-Ping; Ding, Xue-Ying; Guo, Shi-Qi; Wang, Hui-Ying; Liu, Wei-Jia; Jiang, Hui-Min; Li, Ya-Dong; Fu, Ping; Chen, Ping; Mei, Yu-Shuo; Zhang, Guo; Zhou, Hai-Bo; Jing, Jian.
Afiliação
  • Xu JP; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Ding XY; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Guo SQ; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Wang HY; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Liu WJ; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Jiang HM; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Li YD; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Fu P; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Chen P; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Mei YS; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Zhang G; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Chemistry and Biomedicine Innovation Center, Institute for Brain Sciences, Advanced Institute for Life Sciences, School of Life Sciences, Chinese Academy of Medical Scien
  • Zhou HB; School of Electronic Science and Engineering, Nanjing University, Nanjing, Jiangsu, China.
  • Jing J; Peng Cheng Laboratory, Shenzhen, China.
Front Pharmacol ; 14: 1132066, 2023.
Article em En | MEDLINE | ID: mdl-37021048
The vasopressin/oxytocin signaling system is present in both protostomes and deuterostomes and plays various physiological roles. Although there were reports for both vasopressin-like peptides and receptors in mollusc Lymnaea and Octopus, no precursor or receptors have been described in mollusc Aplysia. Here, through bioinformatics, molecular and cellular biology, we identified both the precursor and two receptors for Aplysia vasopressin-like peptide, which we named Aplysia vasotocin (apVT). The precursor provides evidence for the exact sequence of apVT, which is identical to conopressin G from cone snail venom, and contains 9 amino acids, with two cysteines at position 1 and 6, similar to nearly all vasopressin-like peptides. Through inositol monophosphate (IP1) accumulation assay, we demonstrated that two of the three putative receptors we cloned from Aplysia cDNA are true receptors for apVT. We named the two receptors as apVTR1 and apVTR2. We then determined the roles of post-translational modifications (PTMs) of apVT, i.e., the disulfide bond between two cysteines and the C-terminal amidation on receptor activity. Both the disulfide bond and amidation were critical for the activation of the two receptors. Cross-activity with conopressin S, annetocin from an annelid, and vertebrate oxytocin showed that although all three ligands can activate both receptors, the potency of these peptides differed depending on their residue variations from apVT. We, therefore, tested the roles of each residue through alanine substitution and found that each substitution could reduce the potency of the peptide analog, and substitution of the residues within the disulfide bond tended to have a larger impact on receptor activity than the substitution of those outside the bond. Moreover, the two receptors had different sensitivities to the PTMs and single residue substitutions. Thus, we have characterized the Aplysia vasotocin signaling system and showed how the PTMs and individual residues in the ligand contributed to receptor activity.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article