Subcellular proteomic analysis of the DDR2 interactome in a neuronal cell model exposed to Aβ42
Russa Das1, Debashis Mukhopadhyay1
1Biophysical Science Division, Saha Institute of Nuclear Physics, A CI of Homi Bhabha National Institute, 1/AF Bidhannagar, Kolkata 700064, India.
Abstract:
Receptor tyrosine kinases (RTKs) are increasingly understood to signal beyond the plasma membrane. However, the role of Discoidin domain receptor 2 (DDR2), which is activated by collagen, in neurodegeneration remains poorly understood. This study uses immunoprecipitation followed by mass spectrometry on cytoplasmic and nuclear fractions from a neuronal cell model to show that Aβ42 exposure is associated with a compartment-specific reorganization of DDR2-associated protein complexes, characterized by increased nuclear representation. This reveals a unique nuclear DDR2 interactome under amyloidogenic conditions. By exploring this non-canonical, compartment-specific DDR2 signaling pathway, our results offer new insights into how receptor signaling networks may be altered in Alzheimer's disease pathology. Additionally, we identify DDR2-related nuclear interactions as potential sites of dysregulation in neurodegeneration.
Insights
Discoidin domain receptor 2 (DDR2) signaling is altered in Alzheimer's disease models. Aβ42 exposure reorganizes DDR2 protein complexes, increasing their nuclear presence and revealing new insights into neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Receptor tyrosine kinases (RTKs) are known to signal beyond the plasma membrane.
- The role of Discoidin domain receptor 2 (DDR2), activated by collagen, in neurodegeneration is not well understood.
Purpose of the Study:
- To investigate the role and signaling of DDR2 in neurodegeneration.
- To explore the DDR2 interactome in neuronal cells under amyloidogenic conditions.
Main Methods:
- Immunoprecipitation followed by mass spectrometry was performed on cytoplasmic and nuclear fractions.
- A neuronal cell model was used to study the effects of Aβ42 exposure.
Main Results:
- Aβ42 exposure led to a compartment-specific reorganization of DDR2-associated protein complexes.
- Increased nuclear representation of DDR2-associated proteins was observed under amyloidogenic conditions.
- A unique nuclear DDR2 interactome was identified under these conditions.
Conclusions:
- The study reveals a non-canonical, compartment-specific DDR2 signaling pathway.
- Findings offer new insights into altered receptor signaling networks in Alzheimer's disease pathology.
- DDR2-related nuclear interactions are identified as potential sites of dysregulation in neurodegeneration.
More Related Videos
06:23Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons
Published on: October 30, 2018
11:57Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase
Published on: June 24, 2025