Related Experiment Video
Updated: Jul 13, 2025
08:37
Purification of the Sarco-Endoplasmic Reticulum Ca2+-ATPase from Rabbit Muscle
Published on: March 21, 2025
327
Polyarginine Cell-Penetrating Peptides Bind and Inhibit SERCA2
Per Kristian Lunde1, Ornella Manfra1, Thea Parsberg Støle1
1Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway.
Cells
|October 13, 2023
Summary
Polyarginine cell-penetrating peptides (CPPs) inhibit SERCA2, impacting calcium handling. Researchers recommend caution with polyarginine CPPs due to potential off-target effects on SERCA2 activity in various cell types.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Cell-penetrating peptides (CPPs) facilitate cellular entry for cargo delivery.
- Robust screening for off-target effects of CPPs is often lacking.
- Understanding CPP interactions is crucial for safe and effective applications.
Purpose of the Study:
- To investigate off-target effects of commonly used CPPs (TAT, polyarginines) on cellular calcium homeostasis.
- To determine the specific mechanism and target of polyarginine-induced cellular effects.
- To assess the impact on sarcoplasmic reticulum calcium handling.
Main Methods:
- Experiments using cardiac and skeletal muscle myocytes and homogenates.
- HEK cell transfections with specific SERCA isoforms.
- ELISA and Surface Plasmon Resonance (SPR) for protein interaction analysis.
Main Results:
- Polyarginine CPPs, but not TAT, inhibited sarcoplasmic reticulum (SR) Ca2+ uptake by targeting SERCA2a and SERCA2b.
- Inhibition was independent of phospholamban.
- Direct interaction between polyarginines and the SERCA2 actuator domain was confirmed.
Conclusions:
- Polyarginine CPPs directly inhibit SERCA2 activity, affecting cellular calcium homeostasis.
- The findings necessitate caution when using polyarginine CPPs in research and therapy.
- Anticipation of widespread consequences due to SERCA2's presence in diverse cell types is advised.
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