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insight - Computational Biology - # Identification of Juvenile Hormone Cell Membrane Receptors

Receptor Tyrosine Kinases CAD96CA and FGFR1 Function as Cell Membrane Receptors for Insect Juvenile Hormone


Core Concepts
CAD96CA and FGFR1 receptor tyrosine kinases function as cell membrane receptors for insect juvenile hormone, transmitting its signaling for gene expression, calcium increase, and larval development.
Abstract

The content describes the identification of receptor tyrosine kinases (RTKs) CAD96CA and FGFR1 as cell membrane receptors for insect juvenile hormone (JH). Key highlights:

  • Screening of 20 RTKs in the Helicoverpa armigera genome identified CAD96CA and FGFR1 as involved in JH-regulated gene expression, calcium increase, and larval development.
  • Knockout or knockdown of Cad96ca and Fgfr1 genes led to early pupation, decreased JH-induced gene expression, and reduced JH-triggered calcium mobilization.
  • CAD96CA and FGFR1 exhibited high binding affinity to JH III, with dissociation constants of 11.96 nM and 23.61 nM, respectively.
  • Overexpression of CAD96CA and FGFR1 in mammalian HEK-293T cells enabled JH III to trigger rapid calcium increase, confirming their roles as JH cell membrane receptors.
  • JH transmits signals through both the intracellular receptor MET and the cell membrane receptors CAD96CA and FGFR1 at different stages of the signaling pathway.
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Stats
JH III induced a rapid calcium increase in HaEpi cells, which was repressed after knockdown of Vegfr1, Drl, Cad96ca, Nrk, Fgfr1 or Wsck. Knockout of Cad96ca or Fgfr1 in H. armigera larvae led to earlier pupation by about 23-24 hours compared to wild-type. The dissociation constant (Kd) of CAD96CA binding to JH III was 11.96 ± 1.61 nM, and the Kd of FGFR1 binding to JH III was 23.61 ± 0.90 nM.
Quotes
"CAD96CA and FGFR1 transmit JH III signal for gene expression, calcium increase, phosphorylation of MET1 and TAI, and larval status maintaining." "JH III transmits signal by either cell membrane receptor and intracellular receptor at different stages in the signaling, with JH III transmitting the signal by cell membrane receptor CAD96CA and FGFR1 to induce rapid Ca2+ signaling, which regulates the phosphorylation of MET and TAI to enhance the function of MET for gene transcription."

Deeper Inquiries

What other cell surface receptors or signaling pathways might be involved in juvenile hormone signaling beyond CAD96CA and FGFR1?

In addition to CAD96CA and FGFR1, other cell surface receptors and signaling pathways may also play a role in juvenile hormone (JH) signaling. One potential candidate is the G protein-coupled receptors (GPCRs), which have been implicated in JH signaling in various insect species. GPCRs can trigger downstream signaling cascades in response to JH, leading to various physiological effects such as gene expression regulation and calcium mobilization. Additionally, other receptor tyrosine kinases (RTKs) present in insect cells could potentially be involved in JH signaling pathways. These RTKs may interact with JH and transmit signals that regulate gene expression and cellular responses. Further research is needed to explore the specific roles of these receptors and pathways in JH signaling.

How do the binding affinities of CAD96CA and FGFR1 for juvenile hormone compare to their affinities for their known endogenous ligands?

The binding affinities of CAD96CA and FGFR1 for juvenile hormone (JH) compared to their known endogenous ligands can provide insights into the specificity of these receptors for JH. In the study, CAD96CA and FGFR1 were found to have high affinities for JH III, with Kd values of 11.96 nM and 23.61 nM, respectively. These values indicate a strong binding interaction between CAD96CA and FGFR1 with JH III. In comparison, the affinities of CAD96CA and FGFR1 for their known endogenous ligands may vary. For CAD96CA, its affinity for its endogenous ligand is not specified in the context provided. However, for FGFR1, its known endogenous ligand is fibroblast growth factor (FGF). The binding affinity of FGFR1 for FGF may differ from its affinity for JH III, as the receptors can exhibit different binding affinities for various ligands based on their specific structural characteristics and binding sites. Overall, the comparison of the binding affinities of CAD96CA and FGFR1 for JH III and their known endogenous ligands can shed light on the selectivity and specificity of these receptors for different ligands.

Could the identification of juvenile hormone cell membrane receptors lead to the development of new environmentally-friendly insect growth regulators for pest control?

The identification of juvenile hormone (JH) cell membrane receptors, such as CAD96CA and FGFR1, opens up new possibilities for the development of environmentally-friendly insect growth regulators for pest control. By understanding the specific receptors involved in JH signaling, researchers can target these receptors to modulate insect development and behavior in a more precise and targeted manner. Developing agonists or inhibitors that target these JH receptors could provide a novel approach to pest control. By disrupting the JH signaling pathway through these receptors, it may be possible to interfere with key processes such as larval development, metamorphosis, and reproduction in insect pests. This targeted approach could potentially lead to the development of insect growth regulators that are specific to pests, reducing the need for broad-spectrum chemical insecticides and minimizing environmental impact. Overall, the identification of JH cell membrane receptors like CAD96CA and FGFR1 represents a promising avenue for the development of innovative and environmentally-friendly pest control strategies that are more sustainable and effective.
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