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Published on: June 15, 2017
Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments
Akanksha Chaturvedi1, Rebecca Martz, David Dorward
1Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA. achaturvedi@niaid.nih.gov
Nature Immunology
|October 4, 2011
Summary
B cell receptor (BCR) signaling continues after endocytosis, not stopping but moving inside the cell. Blocking BCR endocytosis disrupts kinase activity and gene transcription.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- B cell antigen receptor (BCR) signaling and endocytosis are triggered by antigen binding.
- The regulatory role of endocytosis in BCR signaling remains largely unknown.
Purpose of the Study:
- To investigate how B cell antigen receptor (BCR) endocytosis influences BCR signaling.
- To elucidate the intracellular trafficking and kinase activation dynamics during BCR signaling.
Main Methods:
- Utilized techniques to track BCR trafficking and kinase phosphorylation.
- Employed methods to block B cell antigen receptor (BCR) endocytosis.
- Analyzed the impact on proximal and downstream kinase activation, including mitogen-activated protein kinases (MAPKs) and Akt/Foxo pathways.
Main Results:
- BCR signaling persists intracellularly following endocytosis, involving sequential kinase phosphorylation.
- Inhibition of BCR endocytosis led to aberrant kinase recruitment to the plasma membrane.
- Blocking endocytosis resulted in hyperphosphorylation of mitogen-activated protein kinases (MAPKs) and hypophosphorylation of Akt and Foxo, dysregulating gene transcription.
Conclusions:
- B cell antigen receptor (BCR) endocytosis does not terminate signaling but facilitates its intracellular propagation.
- The cellular localization of the BCR is critical for compartmentalizing kinase activation and regulating signaling outcomes.
- Endocytosis acts as a regulatory mechanism controlling the specificity and fidelity of BCR-mediated gene transcription.
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