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Mitochondrial phosphatase PPTC7 promotes EGFR recycling by facilitating VPS4A endosomal localization
Rahul Baroi1,2, Hilal Ahmad Reshi1,2, SubbaReddy Maddika1
1Laboratory of Cell Death & Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD), Uppal, Hyderabad 500039, India.
Journal of Cell Science
|January 8, 2025
Summary
Protein phosphatase 7 (PPTC7) regulates epidermal growth factor receptor (EGFR) trafficking outside mitochondria. This PPTC7-VPS4A interaction promotes EGFR recycling, enhancing cell growth and migration.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Protein phosphatase 7 (PPTC7) is known for its essential mitochondrial functions.
- However, PPTC7's roles beyond the mitochondria remain largely uncharacterized.
Purpose of the Study:
- To investigate the non-mitochondrial functions of PPTC7.
- To elucidate PPTC7's role in epidermal growth factor receptor (EGFR) trafficking.
Main Methods:
- Co-immunoprecipitation assays to identify protein interactions.
- Western blotting and phospho-specific antibodies to assess protein phosphorylation.
- Immunofluorescence microscopy to determine protein localization.
- EGFR recycling assays and cell proliferation/migration assays.
Main Results:
- PPTC7 interacts with and dephosphorylates VPS4A at serine 335.
- PPTC7-mediated dephosphorylation of VPS4A is crucial for its stability and endosomal localization.
- Loss of PPTC7 or constitutively phosphorylated VPS4A impairs EGFR recycling, leading to lysosomal degradation.
- PPTC7-VPS4A-dependent EGFR recycling activates the AKT signaling pathway, promoting cell proliferation and migration.
Conclusions:
- PPTC7 has a critical non-mitochondrial role in regulating EGFR trafficking via the VPS4A protein.
- The PPTC7-VPS4A complex acts as an endosomal switch, promoting EGFR recycling and downstream signaling.
- This pathway is vital for cellular processes including proliferation and migration.
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